Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising ...Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising strategy to mitigate the adverse effects of prolonged sitting and promote physical activity,ultimately promoting overall health.However,previous ambiguity in defining this concept has resulted in a fragmented and inconsistent evidence base,impeding practical applications,the development of guidelines,and policymaking.The purpose of this study is to establish an operational definition of SBAE by synthesizing systematic reviews and research trials alongside an expert consensus.Additionally,it seeks to evaluate acute and long-term efficacy and feasibility,providing evidence-based recommendations for practice and future research directions.Methods:A literature search was performed across PubMed and Web of Science,followed by systematic screening and summarization of eligible studies based on predefined inclusion criteria.Inclusion criteria encompassed various modes/types of SBAE(bouts lasting≤10 min,performed multiple times daily with≥30 min intervals);both aerobic and resistance exercise were considered.Relevant systematic reviews and research trials were included.Methodological quality,risk of bias,and evidence certainty were assessed.Expert consensus was obtained through a survey to evaluate recommendations and agreement levels on findings.Results:After analyzing 27 systematic reviews,135 research studies,and an expert consensus involving 48 researchers from 11 countries,SBAE is defined as any exercise mode of activity,regardless of intensity,that is accumulated in either continuous or intermittent bouts lasting≤10 min per session(including multiple intermittent sets)that are performed multiple times(≥2 sessions/day)per day,with intervals of≥30 min between bouts or otherwise sufficient time for recovery.When used to interrupt prolonged periods of sedentary time,SBAE mitigates the acute adverse effects of sedentary behavior on more than 10 clinical biomarkers of endocrine,cardiovascular,and brain health/function among adults of diverse ages and conditions.Moreover,SBAE was superior for improving acute glycemic control compared to a single continuous exercise session.As a long-term intervention(average of 11 weeks),SBAE can improve over 20 health outcomes,including peak oxygen uptake,resting blood pressure,and metabolic health.Additionally,SBAE might be more effective than continuous exercise for improving longer-term glycemic control and body composition.Long-term completion rates for SBAE interventions are generally high(95%),with low dropout rates(12%)and high adherence rates even without supervision(85%),and its safety has been preliminarily validated.Conclusion:An operational definition of SBAE is provided along with its classification and acute and long-term efficacy.Practical exercise prescription recommendations and evidence-based strategies for various populations and contexts are provided.Future research should focus on generating high-quality evidence for SBAE in 5 key areas:quantification and monitoring,population-specific responses,optimization of exercise prescriptions,intervention efficacy,and practical implementation.Additionally,addressing policy,environmental,and promotional barriers is crucial for transitioning from expert consensus to public consensus,and for facilitating the application of this strategy in real-world environments.展开更多
Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a s...Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.展开更多
Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially...Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.展开更多
1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal ...1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal evidence that a lack of physical activity,not only has direct effects on the prevalence of non-contagious diseases(NCDs)but has profound additive effects of other risk factors for NCD such as obesity and hypertension.1 The articles in this special topic of Journal of Sport and Health Science(JSHS)are dedicated to research on Exercise biochemistry&metabolism.展开更多
Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly underst...Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly understood.This study aimed to examine the effect of aerobic exercise on structural brain age and to explore potential mediators.Methods:In a single-blind,12-month randomized clinical trial,130 healthy participants aged 26-58 years were randomized into a moderate-to-vigorous intensity aerobic exercise group or a usual-care control group.The exercise group attended two supervised 60-min sessions per week in a laboratory setting plus engaged in home-based exercise to achieve 150 min of exercise per week.Brain-predicted age difference(brain-PAD)and cardiorespiratory fitness(CRF)were assessed at baseline and 12 months.Both intention-to-treat(ITT)and completers analyses(including participants who completed post-intervention assessments)were performed.Results:The 130 participants(67.7%female)had an age of 41.28±9.93 years(mean±SD).At baseline,higher CRF(peak oxygen uptake,VO_(2peak))was associated with smaller brain-PAD(β=-0.309,p=0.012).After the intervention,the exercise group showed a decrease in brainPAD(estimated mean difference(EMD)=-0.60;95%confidence interval(95%CI):-1.15 to-0.04;p=0.034)compared to the control group(EMD=0.35;95%CI:-0.21 to 0.92;p=0.217);time×group interaction(between-group difference(BGD)=-0.95;95%CI:-1.72 to-0.17;p=0.019).VO2peak improved in the exercise group(EMD=1.60;95%CI:0.29-2.90;p=0.017)compared to the control group(EMD=-0.78;95%CI:-2.17 to 0.60;p=0.265);time×group interaction(BGD=2.38;95%CI:0.52-4.25;p=0.015).Body composition,blood pressure,and brain-derived neurotrophic factor levels were unaffected.None of the proposed pathways statistically mediated the effect of exercise on brain-PAD.The results from completers were similar.Conclusion:Engaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults.The pathways by which these effects occur remain unknown.展开更多
Background Obesity is a risk factor for developing cardiometabolic disease.Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality.This study examined the effec...Background Obesity is a risk factor for developing cardiometabolic disease.Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality.This study examined the effect of high-fat feeding on cardiac morphology and mitochondrial function,alongside the mitigating effects of voluntary exercise training.Methods Six-week-old male C57Bl/6 J mice commenced a high fat diet(HFD)or chow diet and were randomized to receive locked(sedentary)or unlocked(voluntary exercise training(VET))running wheels at 10 weeks of age.Mice were monitored until 30 weeks of age and euthanized for collection of tissues.Magnetic resonance imaging was performed to assess body composition,and echocardiography was performed to assess cardiac function.Results Compared with chow-fed animals,the HFD increased body weight and adiposity and decreased cardiolipins(CL)in the heart,which are required for maintaining adequate mitochondrial respiration.Importantly,VET reversed these effects and induced physiological cardiac hypertrophy.Cardiac mitochondrial respiratory chain analysis revealed decreased complexes II and IV activity following high fat feeding,while VET enhanced complex I activity,emphasizing the cardioprotective effect of exercise training in obesity.Conclusion This study uncovers mechanisms by which obesity and exercise impact cardiac mitochondrial health and suggests the mitochondria is a therapeutic target in obesity-related cardiovascular diseases.展开更多
Overweight and obesity are significant public health concerns worldwide due to their association with many chronic health conditions.This has resulted in the development of various interventions focused on weight loss...Overweight and obesity are significant public health concerns worldwide due to their association with many chronic health conditions.This has resulted in the development of various interventions focused on weight loss to reduce the associated health burden.Physical activity is an important lifestyle behavior associated with enhanced health.Evidence supports that many of the benefits of physical activity are realized independent of initial weight status or whether weight loss is achieved,with some benefits additive to what is achieved with weight loss alone.These benefits include enhanced cardiometabolic,brain,cognitive and psychological health,and others.Moreover,in adults with overweight or obesity,physical activity has independent effects on cardiorespiratory fitness,muscular strength,physical function,and mobility.There are also benefits to body composition,with physical activity improving the quality of key tissues,such as skeletal muscle,which may not occur with diet-induced weight loss.Therefore,physical activity is an important public health target for adults with overweight or obesity to provide a wide range of health benefits that extend beyond those of weight loss alone.However,physical activity recommendations and programming efforts should consider the unique characteristics of adults with overweight or obesity to be most effective,and should support a focus on mobility,physical function,and other health outcomes.展开更多
This scoping review aims to synthesize evidence on exercise interventions for adolescents with depression by examining their components and evaluating their effects,thereby informing the development of standardized ex...This scoping review aims to synthesize evidence on exercise interventions for adolescents with depression by examining their components and evaluating their effects,thereby informing the development of standardized exercise programs for this population.Based on the Arksey and O’Malley framework for scoping reviews,the following databases were systematically searched:PubMed,Web of Science,Cochrane Library,Embase,EBSCO,China National Knowledge Infrastructure,Wanfang Database,VIP Database,and China Biomedical Literature Database.Based on the inclusion and exclusion criteria,the original studies applying exercise intervention in adolescents with depression were screened.A total of 9 papers were included,including 7 randomized controlled trials,1 quasi-experimental study,and 1 mixed study.The types of exercise interventions included aerobic exercise,resistance training,anti-gravity exercise,and stretching.The frequency of exercise was 30–60 min,3–5 times per week in most studies,with most intensities being moderate to high.Exercise intervention is feasible and effective in adolescents with depression.Nursing staff play a crucial role in implementing and supervising these interventions,from initial assessment to continuous monitoring of motivation and safety.In future studies,healthcare professionals should focus on assessing the condition and physical functional status of adolescents with depression and improving the specific content of exercise intervention to develop a scientific and standardized exercise training program for adolescents with depression.展开更多
Objective This study aimed to evaluate whether cardiac rehabilitation with a technology-assisted personalized exercise prescription is superior to traditional remote home-based rehabilitation in improving cardiorespir...Objective This study aimed to evaluate whether cardiac rehabilitation with a technology-assisted personalized exercise prescription is superior to traditional remote home-based rehabilitation in improving cardiorespiratory endurance and quality of life in postoperative patients.Methods From October 2022 to April 2024,62 patients who underwent percutaneous coronary intervention for coronary heart disease were recruited from a tertiary hospital in Beijing and randomly assigned to either an intervention group or a control group.After baseline assessments of cardiorespiratory endurance and exercise function,the intervention group received a digitalized personalized exercise prescription combined with remote monitoring rehabilitation.This included an exercise prescription delivered via a mobile application,weekly remote monitoring sessions with an exercise therapist to supervise prescription adherence,provide feedback based on real-time electrocardiographic data,and make personalized adjustments to the exercise prescription based on this information.The control group received an application-delivered exercise movement library and a wearable electrocardiogram device for self-monitoring of exercise intensity.Both groups underwent the 12-week intervention.Changes in maximal oxygen uptake and quality of life were evaluated at enrollment,as well as at 4 weeks,12 weeks,and 24 weeks after the intervention commenced.Results A total of 58 participants completed the study(the intervention group[n=30],the control group[n=28]).Twelve weeks after the interventions,the intervention group showed statistically improvements in VO2AT(Z=2.247,P=0.025),general health(Z=2.126,P=0.033)and social functioning(Z=3.349,P=0.001)compared to the control group.At 24 weeks of follow-up,the intervention group continued to exhibit statistically significant improvements in VO2AT(Z=2.017,P=0.044)and social functioning(Z=3.126,P=0.002).The exercise duration of patients in the intervention group during the exercise test was significantly prolonged at both 4 weeks(Z=−2.420,P=0.021),12 weeks(Z=−2.240,P=0.029)and 24weeks(Z=−2.300,P=0.025)showing statistically significant differences compared to the control group.Conclusions This study provides new evidence-based support for the practical effectiveness of nurses acting as supervisors of rehabilitation implementation and coordinators of multidisciplinary teams within a remote digital cardiac rehabilitation model,underscoring their significant value in the secondary prevention management system for cardiovascular diseases in the information era.展开更多
Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have esta...Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have established that female dams(F0)that perform voluntary wheel running exercise during pregnancy have first-generation(F1)offspring with improved glucose tolerance,suggesting a potential means to reduce the burden of generational metabolic disease transmission.We have shown that maternal exercise also affects F1 male offspring as sires,as their progeny(F2)have similarly improved metabolic health.Whether maternal exercise can affect F1 females in a manner that improves F2 offspring metabolism is not known.Here,we determined whether voluntary exercise by F0 grandmothers,via their F1 female progeny,produced F2 male and female offspring with an improved metabolic phenotype.Methods Six-week-old C57BL/6 N female mice(F0)were fed a chow diet and either kept sedentary or exercise trained by voluntary wheel running for 2 weeks preconception and during pregnancy.Chow-fed sedentary F1 female offspring at 8 weeks of age were bred with age-matched untreated virgin males to generate F2 offspring.F2 were kept sedentary and chow fed and studied up to 52 weeks of age.Metabolic parameters were assessed,including food intake,body weight,body composition,glucose tolerance,systemic glucose and insulin levels,and liver metabolism.Results Grandmaternal exercise did not significantly alter male and female F2 offspring body weights measured throughout the first year of life,nor was there an effect of grandmaternal exercise on F2 offspring fat mass or lean mass.Remarkably,despite the lack of effect on body weight parameters,grandmaternal exercise resulted in improved glucose tolerance and homeostatic model assessment for insulin resistance(HOMA-IR)in F2 offspring at 52 weeks of age,effects that were more pronounced in male F2 offspring.Conclusion Voluntary wheel running exercise in female mice during pregnancy leads to metabolic improvements in her grand offspring,despite no direct intervention of the intermediate maternal generation.Maternal physical activity during pregnancy may reduce metabolic diseases in later generations.展开更多
Objectives This study aimed to evaluate the effectiveness of a Health Belief Model(HBM)-based electronic education program combined with individualized supervised exercise in improving exercise adherence and pregnancy...Objectives This study aimed to evaluate the effectiveness of a Health Belief Model(HBM)-based electronic education program combined with individualized supervised exercise in improving exercise adherence and pregnancy outcomes among women with gestational hypertension.Methods A randomized controlled trial was conducted from June 2024 to February 2025 at a tertiary hospital in Shenzhen,China.A total of 142 pregnant women diagnosed with gestational hypertension were randomly assigned to either an experimental group or a control group.The experimental group received routine antenatal care plus a 6-week HBM-based e-education intervention delivered via a mobile application and short messaging service(SMS)reminders,complemented by individualized in-person exercise guidance.The control group received routine antenatal care only.After the 6-week intervention,outcomes were assessed using the 6-min walk test,a disease knowledge and attitudes questionnaire,and the Pregnancy Exercise Self-Efficacy Scale.Primary outcomes included exercise adherence,blood pressure control,incidence of preeclampsia,and other pregnancy-related outcomes.Results A total of 129 participants completed the study(the intervention group[n=65],the control group[n=64]).At 6 weeks post-intervention,the experimental group demonstrated significantly greater improvements than the control group in exercise adherence,blood pressure control,preeclampsia incidence,disease-related knowledge and attitudes,and exercise self-efficacy(all P<0.05).Specifically,participants in the experimental group engaged in more frequent and longer-duration exercise sessions(P<0.05).Their blood pressure was maintained within a more stable and clinically optimal range(systolic:135.2±4.7 mmHg;diastolic:85.4±4.5 mmHg),which was significantly better than that of the control group(systolic:138.4±10.4 mmHg;diastolic:90.9±6.9 mmHg;P<0.05).The incidence of preeclampsia was also significantly lower in the experimental group(P<0.05).Additionally,scores for disease knowledge,attitudes,and exercise self-efficacy were higher in the experimental group(P<0.05).Within-group comparisons revealed that the experimental group showed significant improvements from baseline in exercise frequency,duration,total physical activity,and knowledge/attitude scores(P<0.05),whereas the control group showed no significant changes(P>0.05).Conclusion By embedding video-based education,real-time monitoring,and personalized support into routine prenatal care,this intervention facilitated positive behavioral changes in physical activity among pregnant women.The approach offers a scalable model for clinical nurses to delivering tailored remote exercise support for women with other pregnancy-related complications.展开更多
Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally.Physical exercise,as an effective strategy for improving general health,has been largely reported for it...Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally.Physical exercise,as an effective strategy for improving general health,has been largely reported for its effectiveness in slowing neurodegeneration and increasing brain functional plasticity,particularly in aging brains.However,the underlying mechanisms of exercise in cognitive aging remain largely unclear.Adiponectin,a cell-secreted protein hormone,has recently been found to regulate synaptic plasticity and mediate the antidepressant effects of physical exercise.Studies on the neuroprotective effects of adiponectin have revealed potential innovative treatments for Alzheimer's disease.Here,we reviewed the functions of adiponectin and its receptor in the brains of human and animal models of cognitive impairment.We summarized the role of adiponectin in Alzheimer's disease,focusing on its impact on energy metabolism,insulin resistance,and inflammation.We also discuss how exercise increases adiponectin secretion and its potential benefits for learning and memory.Finally,we highlight the latest research on chemical compounds that mimic exerciseenhanced secretion of adiponectin and its receptor in Alzheimer's disease.展开更多
Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,explorin...Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,exploring effective strategies to promote the repair and regeneration of nerve cells after spinal cord injury is crucial for optimizing patient prognosis.The purpose of this paper is to conduct an in-depth review of the pathological changes in nerve cells after spinal cord injury and to present the state of research on the role of exercise training in promoting the repair and regeneration of nerve cells after spinal cord injury.In terms of the intrinsic growth capacity of neurons,disruptions in the dynamic balance between growth cones and the cytoskeleton,the dysregulation of transcription factors,abnormal protein signaling transduction,and altered epigenetic modifications collectively hinder axonal regeneration.Additionally,the microenvironment of neurons undergoes a series of complex changes,initially manifesting as edema,which may be exacerbated by spinal cord ischemia-reperfusion injury,further increasing the extent of nerve cell damage.The abnormal proliferation of astrocytes leads to the formation of glial scars,creating a physical barrier to nerve regeneration.The inflammatory response triggered by the excessive activation of microglia negatively impacts the process of nerve repair.Non-invasive interventions involving exercise training have shown significant potential in promoting nerve repair as part of a comprehensive treatment strategy for spinal cord injury.Specifically,exercise training can reshape the growth cone and cytoskeletal structures of neurons,regulate transcription factor activity,modulate protein signaling pathways,and influence epigenetic modifications,thereby activating the intrinsic repair mechanisms of neurons.Moreover,exercise training can regulate the activation state of astrocytes,optimize the inflammatory response and metabolic processes,promote astrocyte polarization,enhance angiogenesis,reduce glial scar formation,and modulate the expression levels of nerve growth factors.It also effectively helps regulate microglial activation,promotes axonal regeneration,and improves phagocytic function,thereby optimizing the microenvironment for nerve repair.In terms of clinical translation,we summarize the preliminary results of new drug research and development efforts,the development of innovative devices,and the use of exercise training in promoting clinical advancements in nerve repair following spinal cord injury,while considering their limitations and future application prospects.In summary,this review systematically analyzes findings relating to the pathological changes occurring in nerve cells after spinal cord injury and emphasizes the critical role of exercise training in facilitating the repair and regeneration of nerve cells.This work is expected to provide new ideas and methods for the rehabilitation of patients with spinal cord injury.展开更多
White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet li...White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.展开更多
Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM),a chronic metabolic disease with a high global incidence,has become a serious public health challenge.China has the largest number of T2DM patients worldwide,imposing a signif...BACKGROUND Type 2 diabetes mellitus(T2DM),a chronic metabolic disease with a high global incidence,has become a serious public health challenge.China has the largest number of T2DM patients worldwide,imposing a significant economic burden on the healthcare system.T2DM is closely associated with insulin resistance,impaired pancreatic B cell function,and disordered glucose and lipid metabolism,which can lead to various complications,reducing patients'quality of life and increasing the risk of disability and death.Thus,finding effective preventive and intervention measures is crucial.Exercise therapy,a key part of diabetes management,has gained attention in recent years,with many studies indicating its benefits for blood glucose control and other aspects in diabetic patients.AIM To assess the effectiveness of combined resistance and aerobic exercise interventions on blood glucose control and metabolic indicators in patients with T2DM and to explore their application in diabetes management.METHODS Systematic searches were conducted using PubMed,EMBASE,Cochrane Library,and Chinese databases for relevant randomized controlled trials(RCTs).The inclusion criteria were participants aged≥18 years with T2DM and the intervention involved combined resistance and aerobic exercise for≥8 weeks.The primary outcome indicators were fasting blood glucose,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),glycated hemoglobin A1c(HbA1c),and total cholesterol(TC)levels.Data analysis was performed using RevMan software,and the interventional effects were assessed using weighted mean differences or standardized mean differences(SMD).RESULTS Six RCTs meeting the inclusion criteria were included,with a total sample size of 366 participants.The meta-analysis results showed that combined resistance and aerobic exercise significantly improved several metabolic indicators in patients with T2DM.Specific results were as follows:(1)For fasting blood glucose,combined exercise was more effective than aerobic exercise alone[SMD=1.22;95%confidence interval(95%CI):0.70,1.74;P<0.00001];(2)LDL-C levels were significantly reduced by the combined intervention(SMD=1.45;95%CI:1.18-1.72;P<0.00001);(3)The combined intervention significantly increased HDL-C levels(SMD=1.42;95%CI:0.98-1.87;P<0.00001);(4)The combined intervention significantly reduced TG levels(SMD=1.12;95%CI:0.85-1.39;P<0.00001;(5)No statistically significant difference was observed in HbA1c between the combined and the aerobic exercise group(SMD=-0.03;95%CI:-1.09 to 1.04;P<0.00001);and(6)The combined exercise intervention group significantly reduced TC levels(SMD=2.66;95%CI:1.93-3.38;P<0.00001).The subgroup analysis results suggest that the effect of exercise interventions may be influenced by various factors,including the patient's age,baseline blood glucose levels,and exercise intensity.CONCLUSION Combined resistance and aerobic exercise intervention significantly improved fasting blood glucose,LDL-C,HDL-C,TG,and TC levels in patients with T2DM,especially in terms of blood glucose control and cardiovascular risk,demonstrating better outcomes than aerobic exercise alone.展开更多
Background:Acute myocardial infarction(AMI)remains the leading form of cardiovascular morbidity and mortality,while exercise is a preventative and therapeutic countermeasure.The collective benefits of exercise on the ...Background:Acute myocardial infarction(AMI)remains the leading form of cardiovascular morbidity and mortality,while exercise is a preventative and therapeutic countermeasure.The collective benefits of exercise on the heart are called cardioprotection.Exercise-induced cardioprotection encompasses four broad areas:1)cardiovascular disease(CVD)risk factor improvement,2)anatomical remodeling of the heart,3)improved cardiac physiologic function,and 4)mechanisms of exercise preconditioning.Discussion:With respect to the latter area of cardioprotection,research indicates that a few days of moderate intensity aerobic exercise preconditions the heart against cardiac dysrhythmias,ventricular pump dysfunction,and tissue death.The short duration protective timeframe,hours to days after exercise,indicates that the mechanisms are biochemical in nature.Protective mechanisms within exercised hearts include endogenous antioxidant enzymes,better regulation of cytosolic Ca2þ,and more efficient bioenergetics.However,a formative body of work conducted over the last decade indicates that additional exogenous mechanisms may be receptor mediated,presumably providing cardioprotection via circulating factors.Preliminary findings indicate that tissueto-tissue cross talk involves cardioprotective paracrine factors derived from muscle or autocrine factors originating from the heart itself.This protection is termed exogenous(or remote)cardiac preconditioning,and appears to includeδ-opioid receptors,IL-6 receptors,and perhaps other surface receptors on exercised cardiac tissue.Conclusion:The current review outlines existing knowledge on exercise and factors of cardiac preconditioning,and highlights the avenues for next-step scientific advances to understanding treatments against AMI.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
文摘Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising strategy to mitigate the adverse effects of prolonged sitting and promote physical activity,ultimately promoting overall health.However,previous ambiguity in defining this concept has resulted in a fragmented and inconsistent evidence base,impeding practical applications,the development of guidelines,and policymaking.The purpose of this study is to establish an operational definition of SBAE by synthesizing systematic reviews and research trials alongside an expert consensus.Additionally,it seeks to evaluate acute and long-term efficacy and feasibility,providing evidence-based recommendations for practice and future research directions.Methods:A literature search was performed across PubMed and Web of Science,followed by systematic screening and summarization of eligible studies based on predefined inclusion criteria.Inclusion criteria encompassed various modes/types of SBAE(bouts lasting≤10 min,performed multiple times daily with≥30 min intervals);both aerobic and resistance exercise were considered.Relevant systematic reviews and research trials were included.Methodological quality,risk of bias,and evidence certainty were assessed.Expert consensus was obtained through a survey to evaluate recommendations and agreement levels on findings.Results:After analyzing 27 systematic reviews,135 research studies,and an expert consensus involving 48 researchers from 11 countries,SBAE is defined as any exercise mode of activity,regardless of intensity,that is accumulated in either continuous or intermittent bouts lasting≤10 min per session(including multiple intermittent sets)that are performed multiple times(≥2 sessions/day)per day,with intervals of≥30 min between bouts or otherwise sufficient time for recovery.When used to interrupt prolonged periods of sedentary time,SBAE mitigates the acute adverse effects of sedentary behavior on more than 10 clinical biomarkers of endocrine,cardiovascular,and brain health/function among adults of diverse ages and conditions.Moreover,SBAE was superior for improving acute glycemic control compared to a single continuous exercise session.As a long-term intervention(average of 11 weeks),SBAE can improve over 20 health outcomes,including peak oxygen uptake,resting blood pressure,and metabolic health.Additionally,SBAE might be more effective than continuous exercise for improving longer-term glycemic control and body composition.Long-term completion rates for SBAE interventions are generally high(95%),with low dropout rates(12%)and high adherence rates even without supervision(85%),and its safety has been preliminarily validated.Conclusion:An operational definition of SBAE is provided along with its classification and acute and long-term efficacy.Practical exercise prescription recommendations and evidence-based strategies for various populations and contexts are provided.Future research should focus on generating high-quality evidence for SBAE in 5 key areas:quantification and monitoring,population-specific responses,optimization of exercise prescriptions,intervention efficacy,and practical implementation.Additionally,addressing policy,environmental,and promotional barriers is crucial for transitioning from expert consensus to public consensus,and for facilitating the application of this strategy in real-world environments.
基金supported by grants from The National Natural Science Foundation of China(82472611)The“14th Five Year Plan”Scientific Research and Innovation Team of Chengdu Sport University(23CXTD02)Sports Medicine Key Laboratory of Sichuan Province/Key Laboratory of Sports Medicine,General Administration of Sport of China(2025-A028)。
文摘Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.
基金supported by the National Key Research and Development Project(2022YFA1104500 to JX)the National Natural Science Foundation of China(82020108002 and82225005 to JX and 82370277 to HW)+1 种基金the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to HW and 23410750100 to JX)supported by a Biotechnology and Biological Sciences Research Council(BBSRC)International Partnering Award。
文摘Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.
文摘1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal evidence that a lack of physical activity,not only has direct effects on the prevalence of non-contagious diseases(NCDs)but has profound additive effects of other risk factors for NCD such as obesity and hypertension.1 The articles in this special topic of Journal of Sport and Health Science(JSHS)are dedicated to research on Exercise biochemistry&metabolism.
基金funded by the National Institutes of Health and the National Heart,Lung,and Blood Institute(P01HL040962)。
文摘Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly understood.This study aimed to examine the effect of aerobic exercise on structural brain age and to explore potential mediators.Methods:In a single-blind,12-month randomized clinical trial,130 healthy participants aged 26-58 years were randomized into a moderate-to-vigorous intensity aerobic exercise group or a usual-care control group.The exercise group attended two supervised 60-min sessions per week in a laboratory setting plus engaged in home-based exercise to achieve 150 min of exercise per week.Brain-predicted age difference(brain-PAD)and cardiorespiratory fitness(CRF)were assessed at baseline and 12 months.Both intention-to-treat(ITT)and completers analyses(including participants who completed post-intervention assessments)were performed.Results:The 130 participants(67.7%female)had an age of 41.28±9.93 years(mean±SD).At baseline,higher CRF(peak oxygen uptake,VO_(2peak))was associated with smaller brain-PAD(β=-0.309,p=0.012).After the intervention,the exercise group showed a decrease in brainPAD(estimated mean difference(EMD)=-0.60;95%confidence interval(95%CI):-1.15 to-0.04;p=0.034)compared to the control group(EMD=0.35;95%CI:-0.21 to 0.92;p=0.217);time×group interaction(between-group difference(BGD)=-0.95;95%CI:-1.72 to-0.17;p=0.019).VO2peak improved in the exercise group(EMD=1.60;95%CI:0.29-2.90;p=0.017)compared to the control group(EMD=-0.78;95%CI:-2.17 to 0.60;p=0.265);time×group interaction(BGD=2.38;95%CI:0.52-4.25;p=0.015).Body composition,blood pressure,and brain-derived neurotrophic factor levels were unaffected.None of the proposed pathways statistically mediated the effect of exercise on brain-PAD.The results from completers were similar.Conclusion:Engaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults.The pathways by which these effects occur remain unknown.
基金MAF is supported by an NHMRC Investigator Grant(APP1194141)Research in his laboratory was supported by project grants from the NHMRC(APP1042465,APP1041760,and APP1156511).
文摘Background Obesity is a risk factor for developing cardiometabolic disease.Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality.This study examined the effect of high-fat feeding on cardiac morphology and mitochondrial function,alongside the mitigating effects of voluntary exercise training.Methods Six-week-old male C57Bl/6 J mice commenced a high fat diet(HFD)or chow diet and were randomized to receive locked(sedentary)or unlocked(voluntary exercise training(VET))running wheels at 10 weeks of age.Mice were monitored until 30 weeks of age and euthanized for collection of tissues.Magnetic resonance imaging was performed to assess body composition,and echocardiography was performed to assess cardiac function.Results Compared with chow-fed animals,the HFD increased body weight and adiposity and decreased cardiolipins(CL)in the heart,which are required for maintaining adequate mitochondrial respiration.Importantly,VET reversed these effects and induced physiological cardiac hypertrophy.Cardiac mitochondrial respiratory chain analysis revealed decreased complexes II and IV activity following high fat feeding,while VET enhanced complex I activity,emphasizing the cardioprotective effect of exercise training in obesity.Conclusion This study uncovers mechanisms by which obesity and exercise impact cardiac mitochondrial health and suggests the mitochondria is a therapeutic target in obesity-related cardiovascular diseases.
基金supported by the National Institutes of Health for the Kansas Center for Metabolism and Obesity Research(award No.P20GM144269)support from the Center for Advancing Translational Sciences of the National Institutes of Health(award No.KL2TR002367)supported by the National Center for Advancing Translational Sciences of the National Institutes of Health(award No.TL1TR002368)。
文摘Overweight and obesity are significant public health concerns worldwide due to their association with many chronic health conditions.This has resulted in the development of various interventions focused on weight loss to reduce the associated health burden.Physical activity is an important lifestyle behavior associated with enhanced health.Evidence supports that many of the benefits of physical activity are realized independent of initial weight status or whether weight loss is achieved,with some benefits additive to what is achieved with weight loss alone.These benefits include enhanced cardiometabolic,brain,cognitive and psychological health,and others.Moreover,in adults with overweight or obesity,physical activity has independent effects on cardiorespiratory fitness,muscular strength,physical function,and mobility.There are also benefits to body composition,with physical activity improving the quality of key tissues,such as skeletal muscle,which may not occur with diet-induced weight loss.Therefore,physical activity is an important public health target for adults with overweight or obesity to provide a wide range of health benefits that extend beyond those of weight loss alone.However,physical activity recommendations and programming efforts should consider the unique characteristics of adults with overweight or obesity to be most effective,and should support a focus on mobility,physical function,and other health outcomes.
文摘This scoping review aims to synthesize evidence on exercise interventions for adolescents with depression by examining their components and evaluating their effects,thereby informing the development of standardized exercise programs for this population.Based on the Arksey and O’Malley framework for scoping reviews,the following databases were systematically searched:PubMed,Web of Science,Cochrane Library,Embase,EBSCO,China National Knowledge Infrastructure,Wanfang Database,VIP Database,and China Biomedical Literature Database.Based on the inclusion and exclusion criteria,the original studies applying exercise intervention in adolescents with depression were screened.A total of 9 papers were included,including 7 randomized controlled trials,1 quasi-experimental study,and 1 mixed study.The types of exercise interventions included aerobic exercise,resistance training,anti-gravity exercise,and stretching.The frequency of exercise was 30–60 min,3–5 times per week in most studies,with most intensities being moderate to high.Exercise intervention is feasible and effective in adolescents with depression.Nursing staff play a crucial role in implementing and supervising these interventions,from initial assessment to continuous monitoring of motivation and safety.In future studies,healthcare professionals should focus on assessing the condition and physical functional status of adolescents with depression and improving the specific content of exercise intervention to develop a scientific and standardized exercise training program for adolescents with depression.
文摘Objective This study aimed to evaluate whether cardiac rehabilitation with a technology-assisted personalized exercise prescription is superior to traditional remote home-based rehabilitation in improving cardiorespiratory endurance and quality of life in postoperative patients.Methods From October 2022 to April 2024,62 patients who underwent percutaneous coronary intervention for coronary heart disease were recruited from a tertiary hospital in Beijing and randomly assigned to either an intervention group or a control group.After baseline assessments of cardiorespiratory endurance and exercise function,the intervention group received a digitalized personalized exercise prescription combined with remote monitoring rehabilitation.This included an exercise prescription delivered via a mobile application,weekly remote monitoring sessions with an exercise therapist to supervise prescription adherence,provide feedback based on real-time electrocardiographic data,and make personalized adjustments to the exercise prescription based on this information.The control group received an application-delivered exercise movement library and a wearable electrocardiogram device for self-monitoring of exercise intensity.Both groups underwent the 12-week intervention.Changes in maximal oxygen uptake and quality of life were evaluated at enrollment,as well as at 4 weeks,12 weeks,and 24 weeks after the intervention commenced.Results A total of 58 participants completed the study(the intervention group[n=30],the control group[n=28]).Twelve weeks after the interventions,the intervention group showed statistically improvements in VO2AT(Z=2.247,P=0.025),general health(Z=2.126,P=0.033)and social functioning(Z=3.349,P=0.001)compared to the control group.At 24 weeks of follow-up,the intervention group continued to exhibit statistically significant improvements in VO2AT(Z=2.017,P=0.044)and social functioning(Z=3.126,P=0.002).The exercise duration of patients in the intervention group during the exercise test was significantly prolonged at both 4 weeks(Z=−2.420,P=0.021),12 weeks(Z=−2.240,P=0.029)and 24weeks(Z=−2.300,P=0.025)showing statistically significant differences compared to the control group.Conclusions This study provides new evidence-based support for the practical effectiveness of nurses acting as supervisors of rehabilitation implementation and coordinators of multidisciplinary teams within a remote digital cardiac rehabilitation model,underscoring their significant value in the secondary prevention management system for cardiovascular diseases in the information era.
基金supported by NIH awards R01 DK101043 to LJG and P30 DK036836 to Joslin Diabetes Centersupported by American Diabetes Association Grant No.1-17-PMF-009+1 种基金supported by American Diabetes Association(Grant No.1-25-PDF-67)supported by fellowships from Sunstar Foundation,Japan Society for the Promotion of Science(JSPS),Kanae Foundation,and Meiji Yasuda Life Foundation of Health and Welfare.
文摘Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have established that female dams(F0)that perform voluntary wheel running exercise during pregnancy have first-generation(F1)offspring with improved glucose tolerance,suggesting a potential means to reduce the burden of generational metabolic disease transmission.We have shown that maternal exercise also affects F1 male offspring as sires,as their progeny(F2)have similarly improved metabolic health.Whether maternal exercise can affect F1 females in a manner that improves F2 offspring metabolism is not known.Here,we determined whether voluntary exercise by F0 grandmothers,via their F1 female progeny,produced F2 male and female offspring with an improved metabolic phenotype.Methods Six-week-old C57BL/6 N female mice(F0)were fed a chow diet and either kept sedentary or exercise trained by voluntary wheel running for 2 weeks preconception and during pregnancy.Chow-fed sedentary F1 female offspring at 8 weeks of age were bred with age-matched untreated virgin males to generate F2 offspring.F2 were kept sedentary and chow fed and studied up to 52 weeks of age.Metabolic parameters were assessed,including food intake,body weight,body composition,glucose tolerance,systemic glucose and insulin levels,and liver metabolism.Results Grandmaternal exercise did not significantly alter male and female F2 offspring body weights measured throughout the first year of life,nor was there an effect of grandmaternal exercise on F2 offspring fat mass or lean mass.Remarkably,despite the lack of effect on body weight parameters,grandmaternal exercise resulted in improved glucose tolerance and homeostatic model assessment for insulin resistance(HOMA-IR)in F2 offspring at 52 weeks of age,effects that were more pronounced in male F2 offspring.Conclusion Voluntary wheel running exercise in female mice during pregnancy leads to metabolic improvements in her grand offspring,despite no direct intervention of the intermediate maternal generation.Maternal physical activity during pregnancy may reduce metabolic diseases in later generations.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2025A1515011703).
文摘Objectives This study aimed to evaluate the effectiveness of a Health Belief Model(HBM)-based electronic education program combined with individualized supervised exercise in improving exercise adherence and pregnancy outcomes among women with gestational hypertension.Methods A randomized controlled trial was conducted from June 2024 to February 2025 at a tertiary hospital in Shenzhen,China.A total of 142 pregnant women diagnosed with gestational hypertension were randomly assigned to either an experimental group or a control group.The experimental group received routine antenatal care plus a 6-week HBM-based e-education intervention delivered via a mobile application and short messaging service(SMS)reminders,complemented by individualized in-person exercise guidance.The control group received routine antenatal care only.After the 6-week intervention,outcomes were assessed using the 6-min walk test,a disease knowledge and attitudes questionnaire,and the Pregnancy Exercise Self-Efficacy Scale.Primary outcomes included exercise adherence,blood pressure control,incidence of preeclampsia,and other pregnancy-related outcomes.Results A total of 129 participants completed the study(the intervention group[n=65],the control group[n=64]).At 6 weeks post-intervention,the experimental group demonstrated significantly greater improvements than the control group in exercise adherence,blood pressure control,preeclampsia incidence,disease-related knowledge and attitudes,and exercise self-efficacy(all P<0.05).Specifically,participants in the experimental group engaged in more frequent and longer-duration exercise sessions(P<0.05).Their blood pressure was maintained within a more stable and clinically optimal range(systolic:135.2±4.7 mmHg;diastolic:85.4±4.5 mmHg),which was significantly better than that of the control group(systolic:138.4±10.4 mmHg;diastolic:90.9±6.9 mmHg;P<0.05).The incidence of preeclampsia was also significantly lower in the experimental group(P<0.05).Additionally,scores for disease knowledge,attitudes,and exercise self-efficacy were higher in the experimental group(P<0.05).Within-group comparisons revealed that the experimental group showed significant improvements from baseline in exercise frequency,duration,total physical activity,and knowledge/attitude scores(P<0.05),whereas the control group showed no significant changes(P>0.05).Conclusion By embedding video-based education,real-time monitoring,and personalized support into routine prenatal care,this intervention facilitated positive behavioral changes in physical activity among pregnant women.The approach offers a scalable model for clinical nurses to delivering tailored remote exercise support for women with other pregnancy-related complications.
基金supported by the National Natural Science Foundation of China,No.82072529(to HWHT)Key Laboratory of Guangdong Higher Education Institutes,No.2021KSYS009(to HWHT)the China Postdoctoral Science Foundation,No.2022M720907(to HHG)。
文摘Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally.Physical exercise,as an effective strategy for improving general health,has been largely reported for its effectiveness in slowing neurodegeneration and increasing brain functional plasticity,particularly in aging brains.However,the underlying mechanisms of exercise in cognitive aging remain largely unclear.Adiponectin,a cell-secreted protein hormone,has recently been found to regulate synaptic plasticity and mediate the antidepressant effects of physical exercise.Studies on the neuroprotective effects of adiponectin have revealed potential innovative treatments for Alzheimer's disease.Here,we reviewed the functions of adiponectin and its receptor in the brains of human and animal models of cognitive impairment.We summarized the role of adiponectin in Alzheimer's disease,focusing on its impact on energy metabolism,insulin resistance,and inflammation.We also discuss how exercise increases adiponectin secretion and its potential benefits for learning and memory.Finally,we highlight the latest research on chemical compounds that mimic exerciseenhanced secretion of adiponectin and its receptor in Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,No.81641048Research Project of Yan’an University,No.2023JBZR-011(both to LZ).
文摘Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,exploring effective strategies to promote the repair and regeneration of nerve cells after spinal cord injury is crucial for optimizing patient prognosis.The purpose of this paper is to conduct an in-depth review of the pathological changes in nerve cells after spinal cord injury and to present the state of research on the role of exercise training in promoting the repair and regeneration of nerve cells after spinal cord injury.In terms of the intrinsic growth capacity of neurons,disruptions in the dynamic balance between growth cones and the cytoskeleton,the dysregulation of transcription factors,abnormal protein signaling transduction,and altered epigenetic modifications collectively hinder axonal regeneration.Additionally,the microenvironment of neurons undergoes a series of complex changes,initially manifesting as edema,which may be exacerbated by spinal cord ischemia-reperfusion injury,further increasing the extent of nerve cell damage.The abnormal proliferation of astrocytes leads to the formation of glial scars,creating a physical barrier to nerve regeneration.The inflammatory response triggered by the excessive activation of microglia negatively impacts the process of nerve repair.Non-invasive interventions involving exercise training have shown significant potential in promoting nerve repair as part of a comprehensive treatment strategy for spinal cord injury.Specifically,exercise training can reshape the growth cone and cytoskeletal structures of neurons,regulate transcription factor activity,modulate protein signaling pathways,and influence epigenetic modifications,thereby activating the intrinsic repair mechanisms of neurons.Moreover,exercise training can regulate the activation state of astrocytes,optimize the inflammatory response and metabolic processes,promote astrocyte polarization,enhance angiogenesis,reduce glial scar formation,and modulate the expression levels of nerve growth factors.It also effectively helps regulate microglial activation,promotes axonal regeneration,and improves phagocytic function,thereby optimizing the microenvironment for nerve repair.In terms of clinical translation,we summarize the preliminary results of new drug research and development efforts,the development of innovative devices,and the use of exercise training in promoting clinical advancements in nerve repair following spinal cord injury,while considering their limitations and future application prospects.In summary,this review systematically analyzes findings relating to the pathological changes occurring in nerve cells after spinal cord injury and emphasizes the critical role of exercise training in facilitating the repair and regeneration of nerve cells.This work is expected to provide new ideas and methods for the rehabilitation of patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82172546(to XH),82172547(to ZZ)the Natural ScienceFoundation of Guangdong Province,Nos.2023A1515012695(to XH),2024A1515010419(to ZZ)the Science and Technology Plan Project of Guangzhou,Nos.202201020413(to ZZ),2023A04J1099(to ZZ).
文摘White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
基金Supported by Research Project of Zhejiang Provincial Science and Technology Plan for Traditional Chinese Medicine,No.2024ZL753and Research Project of Zhejiang Provincial Medical and Health Science and Technology Plan,No.2024KY1406.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM),a chronic metabolic disease with a high global incidence,has become a serious public health challenge.China has the largest number of T2DM patients worldwide,imposing a significant economic burden on the healthcare system.T2DM is closely associated with insulin resistance,impaired pancreatic B cell function,and disordered glucose and lipid metabolism,which can lead to various complications,reducing patients'quality of life and increasing the risk of disability and death.Thus,finding effective preventive and intervention measures is crucial.Exercise therapy,a key part of diabetes management,has gained attention in recent years,with many studies indicating its benefits for blood glucose control and other aspects in diabetic patients.AIM To assess the effectiveness of combined resistance and aerobic exercise interventions on blood glucose control and metabolic indicators in patients with T2DM and to explore their application in diabetes management.METHODS Systematic searches were conducted using PubMed,EMBASE,Cochrane Library,and Chinese databases for relevant randomized controlled trials(RCTs).The inclusion criteria were participants aged≥18 years with T2DM and the intervention involved combined resistance and aerobic exercise for≥8 weeks.The primary outcome indicators were fasting blood glucose,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),glycated hemoglobin A1c(HbA1c),and total cholesterol(TC)levels.Data analysis was performed using RevMan software,and the interventional effects were assessed using weighted mean differences or standardized mean differences(SMD).RESULTS Six RCTs meeting the inclusion criteria were included,with a total sample size of 366 participants.The meta-analysis results showed that combined resistance and aerobic exercise significantly improved several metabolic indicators in patients with T2DM.Specific results were as follows:(1)For fasting blood glucose,combined exercise was more effective than aerobic exercise alone[SMD=1.22;95%confidence interval(95%CI):0.70,1.74;P<0.00001];(2)LDL-C levels were significantly reduced by the combined intervention(SMD=1.45;95%CI:1.18-1.72;P<0.00001);(3)The combined intervention significantly increased HDL-C levels(SMD=1.42;95%CI:0.98-1.87;P<0.00001);(4)The combined intervention significantly reduced TG levels(SMD=1.12;95%CI:0.85-1.39;P<0.00001;(5)No statistically significant difference was observed in HbA1c between the combined and the aerobic exercise group(SMD=-0.03;95%CI:-1.09 to 1.04;P<0.00001);and(6)The combined exercise intervention group significantly reduced TC levels(SMD=2.66;95%CI:1.93-3.38;P<0.00001).The subgroup analysis results suggest that the effect of exercise interventions may be influenced by various factors,including the patient's age,baseline blood glucose levels,and exercise intensity.CONCLUSION Combined resistance and aerobic exercise intervention significantly improved fasting blood glucose,LDL-C,HDL-C,TG,and TC levels in patients with T2DM,especially in terms of blood glucose control and cardiovascular risk,demonstrating better outcomes than aerobic exercise alone.
文摘Background:Acute myocardial infarction(AMI)remains the leading form of cardiovascular morbidity and mortality,while exercise is a preventative and therapeutic countermeasure.The collective benefits of exercise on the heart are called cardioprotection.Exercise-induced cardioprotection encompasses four broad areas:1)cardiovascular disease(CVD)risk factor improvement,2)anatomical remodeling of the heart,3)improved cardiac physiologic function,and 4)mechanisms of exercise preconditioning.Discussion:With respect to the latter area of cardioprotection,research indicates that a few days of moderate intensity aerobic exercise preconditions the heart against cardiac dysrhythmias,ventricular pump dysfunction,and tissue death.The short duration protective timeframe,hours to days after exercise,indicates that the mechanisms are biochemical in nature.Protective mechanisms within exercised hearts include endogenous antioxidant enzymes,better regulation of cytosolic Ca2þ,and more efficient bioenergetics.However,a formative body of work conducted over the last decade indicates that additional exogenous mechanisms may be receptor mediated,presumably providing cardioprotection via circulating factors.Preliminary findings indicate that tissueto-tissue cross talk involves cardioprotective paracrine factors derived from muscle or autocrine factors originating from the heart itself.This protection is termed exogenous(or remote)cardiac preconditioning,and appears to includeδ-opioid receptors,IL-6 receptors,and perhaps other surface receptors on exercised cardiac tissue.Conclusion:The current review outlines existing knowledge on exercise and factors of cardiac preconditioning,and highlights the avenues for next-step scientific advances to understanding treatments against AMI.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
