Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
The three-phase Enriched Environment(EE)paradigm has been shown to promote post-stroke functional improvement,but the neuronal mechanisms are still unclear.In this study,we applied a multimodal neuroimaging protocol c...The three-phase Enriched Environment(EE)paradigm has been shown to promote post-stroke functional improvement,but the neuronal mechanisms are still unclear.In this study,we applied a multimodal neuroimaging protocol combining magnetic resonance imaging(MRI)and positron emission tomography(PET)to examine the effects of post-ischemic EE treatment on structural and functional neuroplasticity in the bilateral sensorimotor cortex.Rats were subjected to permanent middle cerebral artery occlusion.The motor function of the rats was examined using the DigiGait test.MRI was applied to investigate the EE-induced structural modifications of the bilateral sensorimotor cortex.[^(18)F]-fluorodeoxyglucose PET was used to detect glucose metabolism.Blood oxygen level-dependent(BOLD)-functional MRI(fMRI)was used to identify the regional brain activity and functional connectivity(FC).In addition,the expression of neuroplasticity-related signaling pathways including neurotrophic factors(BDNF/CREB),axonal guidance proteins(Robo1/Slit2),and axonal growth-inhibitory proteins(NogoA/NgR)as well as downstream proteins(RhoA/ROCK)in the bilateral sensorimotor cortex were measured by Western blots.Our results showed the three-phase EE improved the walking ability.Structural T2 mapping imaging and diffusion tensor imaging demonstrated that EE benefited structure integrity in the bilateral sensorimotor cortex.PET-MRI fused images showed improved glucose metabolism in the corresponding regions after EE intervention.Specifically,the BOLD-based amplitude of low-frequency fluctuations showed that EE increased spontaneous activity in the bilateral motor cortex and ipsilateral sensory cortex.In addition,FC results showed increased sensorimotor connectivity in the ipsilateral hemisphere and increased interhemispheric motor cortical connectivity and motor cortical-thalamic connectivity following EE intervention.In addition,a strong correlation was found between increased functional connectivity and improved motor performance of limbs.Specifically,EE regulated the expression of neuroplasticity-related signaling,involving BDNF/CREB,Slit2/Robo1,as well as the axonal growth–inhibitory pathways Nogo-A/Nogo receptor and RhoA/ROCK in the bilateral sensorimotor cortex.Our results indicated that the three-phase enriched environment paradigm enhances neuronal plasticity of the bilateral sensorimotor cortex and consequently ameliorates post-stroke gait deficits.These findings might provide some new clues for the development of EE and thus facilitate the clinical translation of EE.展开更多
Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neu...Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.展开更多
Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty p...Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty proteases with potent endopeptidase activity.They are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal function.Although cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal plasticity.We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease.Importantly,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury.It is well established that normal cathepsin activity is integral to the function of lysosomes.Without normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy.Furthermore,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity.This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.展开更多
OBJECTIVE:To investigate the effects of acupuncture combined with upper limb rehabilitation robot on neural remodeling and functional recovery in post-stroke patients.METHODS:There were 50 stroke patients were randoml...OBJECTIVE:To investigate the effects of acupuncture combined with upper limb rehabilitation robot on neural remodeling and functional recovery in post-stroke patients.METHODS:There were 50 stroke patients were randomly divided into an experimental group(acupuncture combined with upper limb rehabilitation robot assisted training)and a control group(upper limb rehabilitation robot assisted training).Various assessments were conducted to compare the effects of the two treatments on neural remodeling and functional recovery.Functional near-infrared spectroscopy technology was used to assess the effects of different treatments on neural plasticity and their impact on upper limb function and activities of daily living.RESULTS:The experimental group showed significantly higher concentrations of oxygenated hemoglobin and total hemoglobin in specific brain regions compared to the control group(P<0.05).Additionally,the experimental group had significantly lower concentrations of deoxygenated hemoglobin(P<0.05).After treatment,both groups showed improvements in various measures,but the experimental group had significantly greater improvements(P<0.05).CONCLUSION:Acupuncture combined with upper limb rehabilitation robot can effectively improve upper limb function and neural remodeling in stroke patients.This study supports the integration of Traditional Chinese and Western Medicine in improving limb dysfunction poststroke.展开更多
Despite intense research efforts, the specific pathogenic mechanisms that underlie the link between respiratory syncytial virus （RSV） and childhood asthma remain unclear. Recent researches suggest that changes in th...Despite intense research efforts, the specific pathogenic mechanisms that underlie the link between respiratory syncytial virus （RSV） and childhood asthma remain unclear. Recent researches suggest that changes in the structure and function of the nerves themselves in response to changing conditions, a phenomenon known as neuronal plasticity, may also contribute to the pathophysiology of airway diseases. Therefore.展开更多
The B-cell lymphoma 2 （Bcl2） family of proteins participates in cell death or survival through a mitochondrial pathway. The pro-apoptotic members of the Bcl2 family such as Bim, Bid, Bax and Bak trigger cell death b...The B-cell lymphoma 2 （Bcl2） family of proteins participates in cell death or survival through a mitochondrial pathway. The pro-apoptotic members of the Bcl2 family such as Bim, Bid, Bax and Bak trigger cell death by contributing to the enhancement of mitochondrial outer membrane permeabil- ity to pro-apoptotic factors such as cytochrome c, with the subsequent activation of caspases. The anti-apoptotic mem- bers, such as B-cell lymphoma-extra large （Bd-xL）, block the pro-apoptotic Bcl2 members and prevent cell death. Bcl-xL is abundantly expressed during development and in mature neurons, suggesting that it plays a role in protection from death from untoward events occurring in adult life such as ischemia, inflammation or trauma. When these neurotoxic in- sults occur, Bcl-xL translocates to mitochondria and prevents activation and homo-oligomerization of pro-apoptotic family members such Bax and Bak. Numerous studies have shown pro-survival roles for Bcl-xL in adult neurons using various models; nevertheless, the role of Bcl-xL outside of the field of neuronal death, i.e., in adult neuronal growth, excitability or synaptic plasticity, has not been studied in depth.展开更多
Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticit...Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticity in the motor cortex following cerebral ischemia were published in three issues. We hope that our readers find these papers useful to their research.展开更多
Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target no...Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.展开更多
N-methyl-D-aspartate receptors(NMDARs)play crucial roles in neuronal plasticity and brain function by sensing key neurotransmitters,such as glutamate and glycine.In a tour-de-force,Zhang et al.[1]provide the first ima...N-methyl-D-aspartate receptors(NMDARs)play crucial roles in neuronal plasticity and brain function by sensing key neurotransmitters,such as glutamate and glycine.In a tour-de-force,Zhang et al.[1]provide the first images of native NMDARs directly extracted from rat brains,revealing key aspects of NMDAR assembly and diversity.展开更多
In the contemporary research landscape of mental illness treatment,fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges.Although exposure therapy remains a fundamental ...In the contemporary research landscape of mental illness treatment,fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges.Although exposure therapy remains a fundamental component of treatment,its efficacy varies considerably among individuals.DNA methylation plays a pivotal role in the extinction of fear memories,providing a promising molecular mechanism that could enhance the success of exposure-based interventions.Extensive studies have consistently demonstrated a substantial association between DNA methylation and neuronal plasticity.While DNA methylation holds potential regulatory effects on the effectiveness of exposure therapy,the bidirectional regulatory relationship between it and neuronal activity necessitates addressing several challenges before its widespread clinical application for mental disorders.First,excessive DNA methylation may suppress neural function,and non-selective enhancement of methylation could be counterproductive.Furthermore,due to potential systemic side effects,the use of methylation-modulating agents might disrupt the physiological balance and functionality of other organs and systems.Despite the dynamic interplay between DNA methylation and neuronal activity offering novel insights into the treatment of mental disorders, the strict consideration of target specificity and an appropriate dosing window requirescautious implementation in clinical practice.展开更多
OBJECTIVE:To evaluate the anti-apoptotic efficacy of Qingnao Yizhi formula(清脑益智方,QNYZ)in cultured cerebral cortical neuronal cells(CNCs)and the regulation of the NogoA-Nogo receptor(NgR)/Rho-Rho kinase(ROCK)signa...OBJECTIVE:To evaluate the anti-apoptotic efficacy of Qingnao Yizhi formula(清脑益智方,QNYZ)in cultured cerebral cortical neuronal cells(CNCs)and the regulation of the NogoA-Nogo receptor(NgR)/Rho-Rho kinase(ROCK)signaling pathway.METHODS:Primary cultured CNCs were randomly divided into the following groups:normal control group(N-C),hypoxia-reoxygenation group(H/R),high-dose QNYZ group(Q-H),low-dose QNYZ group(Q-L)butylphthalide(NBP)group,and Y-27632(a selective ROCK transduction pathway inhibiter)group.Except those in the N-C group,CNCs were placed in hypoxic conditions for 24 h and then in reoxygenation conditions for 24 h.Cell media was changed every 48 h,and various assays were performed on the 7 th day.Cell viability was evaluated by measuring mitochondrial dehydrogenase activity,using a CCK-8 assay,in triplicate.Synapsin(SYN)protein concentrations were evaluated by enzyme-linked immunosorbent assay.NogoA and RhoA protein expression were evaluated through Western blotting.The gene expression of NogoA,NgR,RhoA,and ROCK was evaluated by reverse transcription-polymerase chain reaction.Cell apoptosis was measured using a terminal deoxynucleotidyl transferase biotin-d UTP nick end labeling assay.RESULTS:Compared with the N-C group,the cell viability of the H/R group decreased significantly(P<0.05).The cell viability values for the Q-H and Q-L groups increased compared with that for the H/R group,and the difference was significant for the Q-H group(P<0.05).The NogoA and RhoA protein levels and the NogoA,NgR,RhoA,and ROCK m RNA expression levels increased in the H/R group,compared with the N-C group,and decreased significantly in the Q-H and Q-L groups(P<0.05)and in the Y-27632 group(P<0.05)compared with the H/R group.The SYN levels in the Q-H,Q-L,and NBP groups significantly increased compared with that in the H/R group(P<0.05).Compared with the H/R group,the numbers of apoptotic cells in the Q-H,Q-L,and NBP groups significantly decreased(P<0.05).CONCLUSION:The presented study demonstrated that QNYZ exerted anti-apoptotic effects on H/R-induced CNCs,possibly through the modulation of the NogoA-NgR/Rho-ROCK signaling pathway and the promotion of synaptic plasticity in H/R CNCs.展开更多
Various retinal injuries induced by ocular hypertension have been shown to induce plastic changes in retinal synapses, but the potential regulatory mechanism of synaptic plasticity after retinal injury was still uncle...Various retinal injuries induced by ocular hypertension have been shown to induce plastic changes in retinal synapses, but the potential regulatory mechanism of synaptic plasticity after retinal injury was still unclear. A rat model of acute ocular hypertension was established by injecting saline intravitreally for an hour, and elevating the intraocular pressure to 14.63 kPa （110 mmHg）. Western blot assay and immunofluorescence results showed that synaptophysin expression had a distinct spatiotemporal change that increased in the inner plexiform layer within 1 day and spread across the outer plexiform layer after 3 days. Glial fibrillary acidic protein expression in retinae was greatly increased after 3 days, and reached a peak at 7 days, which was also consistent with the peak time of synaptophysin expression in the outer plexiform layer following the increased intraocular pressure. Fluorocitrate, a glial metabolic inhibitor, was intravitreally injected to inhibit glial cell activation following high intraocular pressure. This significantly inhibited the enhanced glial fibrillary acidic protein expression induced by high intraocular pressure injury. Synaptophysin expression also decreased in the inner plexiform layer within a day and the widened distribution in the outer plexiform layer had disappeared by 3 days. The results suggested that retinal glial cell activation might play an important role in the process of retinal synaptic plasticity induced by acute high intraocular pressure through affecting the expression and distribution of synaptic functional proteins, such as synaptophysin.展开更多
AIM:To investigate whether head and neck proprioception and motor control could be compensatory enhanced by long-term vision loss or impairment.METHODS:Individuals who were blind,low vision or sighted were included in...AIM:To investigate whether head and neck proprioception and motor control could be compensatory enhanced by long-term vision loss or impairment.METHODS:Individuals who were blind,low vision or sighted were included in the study,which would undergo the head repositioning test(HRT).The constant error(CE),absolute error(AE),variable error(VE)and root mean square error(RMSE)of each subject were statistically analyzed.Data were analyzed using the SAS 9.4.Tukey-Kramer for one-way ANOVA was used for comparison of blind,low vision,and sighted subjects,as well as to compare subjects with balanced vision,strong vision in the left eye and strong vision in the right eye.Independent sample t-test was used to compare subjects with congenital blindness and acquired blindness,as well as left and right hand dominance subjects.RESULTS:A total of 90 individuals(25 blind subjects,31 low vision subjects,and 34 sighted subjects)were included in the study.Among the blind subjects,14 cases had congenital blindness and 11 cases had acquired blindness.Among the blind and low vision subjects,21 cases had balanced binocular vision,17 cases had strong vision in the left eye and 18 cases had strong vision in the right eye.Among all subjects,11 cases were left hand dominance,and 79 cases were right hand dominance.There were significant differences in AE,VE,and RMSE in head rotation between blind,low vision,and sighted subjects(P<0.01),in AE,VE,and RMSE between blind and sighted(P<0.01),and in VE and RMSE between low vision and sighted(P<0.05).No significant difference between blind and low vision(P>0.05).Significant differences in CE and AE of head right rotation and CE of general head rotation between congenital and acquired(P<0.05).No significant differences between left and right hand dominance and in balance or not of binocular vision(P>0.05).CONCLUSION:Long-term vision loss or impairment does not lead to compensatory enhancement of head and neck proprioception and motor control.Acquired experience contributes to HRT performance in the blind and has long-lasting effects on plasticity in the development of proprioception and sensorimotor control.展开更多
OBJECTIVE:To investigate the efficacy of Jinsiwei(a patented Chinese herbal compound)on learning and memory impairment,the number of synapses and synaptic plasticity-related structural and functional protein expressio...OBJECTIVE:To investigate the efficacy of Jinsiwei(a patented Chinese herbal compound)on learning and memory impairment,the number of synapses and synaptic plasticity-related structural and functional protein expression in mice with sporadic Alzheimer’s disease(SAD)induced by streptozotocin.METHODS:Seventy-five C57/BL6J male mice were intracerebroventricularly injected with streptozotocin to establish the animal model of SAD.Mice were randomly divided into the model group(MG),donepezil group(DG),and the Jinsiwei high,medium,and low-dose groups(JH,JM,JL).Another fifteen C57/BL6J male mice were injected with artificial cerebrospinal fluid as the control group(CG).The intervention groups were intragastrically administrated with corresponding medicine,while the CG and MG were given 0.5%carboxymethyl cellulose by gavage.After 3 months,the Morris Water Maze test and step-down passive avoidance test were used to assess the learning and memory ability of mice.Synapses in hippocampal CA1 were observed by transmission electron microscope.Immunohistochemistry and western blotting were used to assess the distribution and expression levels of synaptic plasticity-related structural and functional proteins involving drebrin,cofilin,synapsin(syn),and N-methyl D-aspartate receptor subtype 2B(NR2B).RESULTS:The Morris Water Maze results showed that the escape latency in the Jinsiwei intervention groups was significantly shorter than that of the MG.Results of the step-down passive-avoidance test showed that the error times in the Jinsiwei intervention groups were significantly reduced compared with the MG.Transmission electron microscope results showed that the number of synapses in hippocampal CA1 was obviously increased in the Jinsiwei intervention groups compared with the MG.Immunohistochemical and western blotting results revealed that the positive cells and expression levels of drebrin,syn,and NR2B were significantly decreased in the MG and meanwhile cofilin significantly increased,while these changes were reversed after the Jinsiwei treatment.CONCLUSIONS:Jinsiwei can alleviate learning and memory impairments in a mouse model of SAD,increase the number of synapses and enhance synaptic plasticity via rescuing the expression of drebrin,syn,and NR2B and inhibiting cofilin expression.展开更多
Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common ...Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.展开更多
The systemic health benefits of regular skeletal muscle activity are well documented.Increased skeletal muscle activity is associated with an improved systemic metabolic state,reduced incidence of diabetes and obesity...The systemic health benefits of regular skeletal muscle activity are well documented.Increased skeletal muscle activity is associated with an improved systemic metabolic state,reduced incidence of diabetes and obesity,and improved function with age.Despite these known systemic benefits,many healthy people do not meet the recommended daily dose of skeletal muscle activity（exercise）needed to prevent systemic metabolic disease,leading to an in-creased prevalence of obesity.展开更多
Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progressio...Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.展开更多
OBJECTIVE:To investigate whether the Chinese massage system,Tuina,exerts analgesic effects in a rat model of chronic constriction injury(CCI)by remodeling the synaptic structure in the spinal cord dorsal horn(SCDH).ME...OBJECTIVE:To investigate whether the Chinese massage system,Tuina,exerts analgesic effects in a rat model of chronic constriction injury(CCI)by remodeling the synaptic structure in the spinal cord dorsal horn(SCDH).METHODS:Sixty-nine male Sprague–Dawley rats were randomly and evenly divided into the normal group,sham group,CCI group,CCI+Tuina group,CCI+MK-801[an N-methyl D-aspartate receptor subtype 2B(NR2B)antagonist]group,and CCI+MK-801+Tuina group.The neuropathic pain model was established using CCI with right sciatic nerve ligation.Tuina was administered 4 d after CCI surgery,using pressing manipulation for 10 min,once daily.Motor function was observed with the inclined plate test,and pain behaviors were observed by the Von Frey test and acetone spray test.At 19 d after surgery,the L3-L5 spinal cord segments were removed.Glutamate,interleukin 1β(IL-1β),and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of NR2B and postsynaptic density protein-95(PSD-95)were detected by Western blot,and the synaptic structure was observed by transmission electron microscopy(TEM).RESULTS:CCI reduced motor function and caused mechanical and cold allodynia in rats,increased glutamate concentration and TNF-αand IL-1βlevels,and increased expression of synapse-related proteins NR2B and PSD-95 in the SCDH.TEM revealed that the synaptic structure of SCDH neurons was altered.Most of these disease-induced changes were reversed by Tuina and intrathecal injection of MK-801(P<0.05 or<0.01).For the majority of experiments,no significant differences were found between the CCI+MK-801 and CCI+MK-801+Tuina groups.CONCLUSIONS:Chinese Tuina can alleviate pain by remodeling the synaptic structure,and NR2B and PSD-95 receptors in the SCDH may be among its targets.展开更多
OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB ...OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB and BDNF/TrkB signaling,as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.METHODS:Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine(PCPA)once daily for 2 d.EA was applied at Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),or Shenmen(HT7)+Baihui(GV20)+Sanyinjiao(SP6)(combined)for 30 min daily for 4 d.Spatial learning and memory function was evaluated by the Morris water maze(MWM)test.Protein expressions of hippocampal cAMP-dependent protein kinase(PKA)-Cβ,phosphorylated cAMP-responsive element-binding protein(p-CREB),brainderived neurotrophic factor(BDNF),and tyrosine kinase receptor B(TrkB)were evaluated by Western blotting.Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay.Endogenous neurogenesis was examined with bromodeoxyuridine staining.The MWM test and hippocampal p-CREB,BDNF,and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor(H89).RESULTS:Spatial learning and memory were significantly impaired in rats with insomnia.The spatial learning deficits were ameliorated in the Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),and combined groups;this improvement was significantly greater in the combined group than the single acupoint groups.The spatial memory impairment was improved in the combined,Baihui(GV20),and Shenmen(HT7)groups,but not the Sanyinjiao(SP6)group.The expressions of PKA-Cβ,p-CREB,BDNF,and TrkB were decreased in rats with insomnia.All these proteins were significantly upregulated in the combined group.PKA/p-CREB protein levels were elevated in the Baihui(GV20)and Shenmen(HT7)groups,whereas BDNF/TrkB expression was upregulated in the Sanyinjiao(SP6)group.The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group,whereas the single acupoint groups only showed decreased numbers of apoptotic cells.In the combined group,the PKA inhibitor reversed the improvement of spatial memory and upregulation of pCREB expression caused by EA,but did not affect its activation of BDNF/TrkB signaling.CONCLUSIONS:EA at the single acupoints Baihui(GV20),Shenmen(HT7),or Sanyinjiao(SP6)had an ameliorating effect on the spatial learning and memory deficits induced by insomnia.EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling,facilitating neurogenesis,and inhibiting neuronal apoptosis.These findings indicate that EA at combined acupoints[(Baihui(GV20),Shenmen(HT7),and Sanyinjiao(SP6)]achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints,which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.展开更多
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
文摘Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
基金supported by the National Natural Science Foundation of China(82174471).
文摘The three-phase Enriched Environment(EE)paradigm has been shown to promote post-stroke functional improvement,but the neuronal mechanisms are still unclear.In this study,we applied a multimodal neuroimaging protocol combining magnetic resonance imaging(MRI)and positron emission tomography(PET)to examine the effects of post-ischemic EE treatment on structural and functional neuroplasticity in the bilateral sensorimotor cortex.Rats were subjected to permanent middle cerebral artery occlusion.The motor function of the rats was examined using the DigiGait test.MRI was applied to investigate the EE-induced structural modifications of the bilateral sensorimotor cortex.[^(18)F]-fluorodeoxyglucose PET was used to detect glucose metabolism.Blood oxygen level-dependent(BOLD)-functional MRI(fMRI)was used to identify the regional brain activity and functional connectivity(FC).In addition,the expression of neuroplasticity-related signaling pathways including neurotrophic factors(BDNF/CREB),axonal guidance proteins(Robo1/Slit2),and axonal growth-inhibitory proteins(NogoA/NgR)as well as downstream proteins(RhoA/ROCK)in the bilateral sensorimotor cortex were measured by Western blots.Our results showed the three-phase EE improved the walking ability.Structural T2 mapping imaging and diffusion tensor imaging demonstrated that EE benefited structure integrity in the bilateral sensorimotor cortex.PET-MRI fused images showed improved glucose metabolism in the corresponding regions after EE intervention.Specifically,the BOLD-based amplitude of low-frequency fluctuations showed that EE increased spontaneous activity in the bilateral motor cortex and ipsilateral sensory cortex.In addition,FC results showed increased sensorimotor connectivity in the ipsilateral hemisphere and increased interhemispheric motor cortical connectivity and motor cortical-thalamic connectivity following EE intervention.In addition,a strong correlation was found between increased functional connectivity and improved motor performance of limbs.Specifically,EE regulated the expression of neuroplasticity-related signaling,involving BDNF/CREB,Slit2/Robo1,as well as the axonal growth–inhibitory pathways Nogo-A/Nogo receptor and RhoA/ROCK in the bilateral sensorimotor cortex.Our results indicated that the three-phase enriched environment paradigm enhances neuronal plasticity of the bilateral sensorimotor cortex and consequently ameliorates post-stroke gait deficits.These findings might provide some new clues for the development of EE and thus facilitate the clinical translation of EE.
文摘Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.
基金JS was funded by NINDS(NS25713)Brumagin-Nelson Fund+1 种基金Kaneko Family Fundthe Hong Kong Spinal Cord Injury Fund.
文摘Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty proteases with potent endopeptidase activity.They are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal function.Although cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal plasticity.We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease.Importantly,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury.It is well established that normal cathepsin activity is integral to the function of lysosomes.Without normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy.Furthermore,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity.This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Project(2024ZL769):Effect of Xingshen Kaiqiao Acupuncture Method combined with Upper Limb Robot-assisted Training on Upper Limb Function and Neuroplasticity Mechanism of Hemiplegia after Stroke based on Functional Near-Infrared Spectroscopy Technology。
文摘OBJECTIVE:To investigate the effects of acupuncture combined with upper limb rehabilitation robot on neural remodeling and functional recovery in post-stroke patients.METHODS:There were 50 stroke patients were randomly divided into an experimental group(acupuncture combined with upper limb rehabilitation robot assisted training)and a control group(upper limb rehabilitation robot assisted training).Various assessments were conducted to compare the effects of the two treatments on neural remodeling and functional recovery.Functional near-infrared spectroscopy technology was used to assess the effects of different treatments on neural plasticity and their impact on upper limb function and activities of daily living.RESULTS:The experimental group showed significantly higher concentrations of oxygenated hemoglobin and total hemoglobin in specific brain regions compared to the control group(P<0.05).Additionally,the experimental group had significantly lower concentrations of deoxygenated hemoglobin(P<0.05).After treatment,both groups showed improvements in various measures,but the experimental group had significantly greater improvements(P<0.05).CONCLUSION:Acupuncture combined with upper limb rehabilitation robot can effectively improve upper limb function and neural remodeling in stroke patients.This study supports the integration of Traditional Chinese and Western Medicine in improving limb dysfunction poststroke.
基金This work was supported by the National Natural Science Foundation of China (No.30470756).
文摘Despite intense research efforts, the specific pathogenic mechanisms that underlie the link between respiratory syncytial virus （RSV） and childhood asthma remain unclear. Recent researches suggest that changes in the structure and function of the nerves themselves in response to changing conditions, a phenomenon known as neuronal plasticity, may also contribute to the pathophysiology of airway diseases. Therefore.
文摘The B-cell lymphoma 2 （Bcl2） family of proteins participates in cell death or survival through a mitochondrial pathway. The pro-apoptotic members of the Bcl2 family such as Bim, Bid, Bax and Bak trigger cell death by contributing to the enhancement of mitochondrial outer membrane permeabil- ity to pro-apoptotic factors such as cytochrome c, with the subsequent activation of caspases. The anti-apoptotic mem- bers, such as B-cell lymphoma-extra large （Bd-xL）, block the pro-apoptotic Bcl2 members and prevent cell death. Bcl-xL is abundantly expressed during development and in mature neurons, suggesting that it plays a role in protection from death from untoward events occurring in adult life such as ischemia, inflammation or trauma. When these neurotoxic in- sults occur, Bcl-xL translocates to mitochondria and prevents activation and homo-oligomerization of pro-apoptotic family members such Bax and Bak. Numerous studies have shown pro-survival roles for Bcl-xL in adult neurons using various models; nevertheless, the role of Bcl-xL outside of the field of neuronal death, i.e., in adult neuronal growth, excitability or synaptic plasticity, has not been studied in depth.
文摘Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticity in the motor cortex following cerebral ischemia were published in three issues. We hope that our readers find these papers useful to their research.
基金supported by the National Natural Science Foundation of China,Nos. 81760247, 82171450the Scientific Research Foundation for Doctors of the Affiliated Hospital of Zunyi Medical University,No.(2016)14 (all to HH)。
文摘Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.
文摘N-methyl-D-aspartate receptors(NMDARs)play crucial roles in neuronal plasticity and brain function by sensing key neurotransmitters,such as glutamate and glycine.In a tour-de-force,Zhang et al.[1]provide the first images of native NMDARs directly extracted from rat brains,revealing key aspects of NMDAR assembly and diversity.
基金Supported by the General Program of the Joint Fund Project Under the Liaoning Provincial Science and Technology Plan,No.2024-MSLH-104Research Project Plan of the Qingpu Branch of Zhongshan Hospital,No.QYT2023-02Research Topic of the Shanghai Qingpu District Health Commission,No.QWJ2024-10.
文摘In the contemporary research landscape of mental illness treatment,fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges.Although exposure therapy remains a fundamental component of treatment,its efficacy varies considerably among individuals.DNA methylation plays a pivotal role in the extinction of fear memories,providing a promising molecular mechanism that could enhance the success of exposure-based interventions.Extensive studies have consistently demonstrated a substantial association between DNA methylation and neuronal plasticity.While DNA methylation holds potential regulatory effects on the effectiveness of exposure therapy,the bidirectional regulatory relationship between it and neuronal activity necessitates addressing several challenges before its widespread clinical application for mental disorders.First,excessive DNA methylation may suppress neural function,and non-selective enhancement of methylation could be counterproductive.Furthermore,due to potential systemic side effects,the use of methylation-modulating agents might disrupt the physiological balance and functionality of other organs and systems.Despite the dynamic interplay between DNA methylation and neuronal activity offering novel insights into the treatment of mental disorders, the strict consideration of target specificity and an appropriate dosing window requirescautious implementation in clinical practice.
基金Supported by the National Natural Science Foundation of China(Study on the Mechanism of NogoA-NgR/Rho-ROCK in Regulating the Synaptic Remodeling of VD,No.81202653)the China Postdoctoral Fund of Sciences(Study on the Mechanism of Qingnao Yizhi Formula Based on the PI3K-Akt-mTOR Signal Transduction Pathway in the Treatment of Vascular Dementia,No.20110490080)+1 种基金Science and Innovation Commission of Shenzhen(Mechanism Study of Hydroxysafflor Yellow A Regulating Mitochondrial Autophagy through ROS Mediated PINK1/parkin Pathway in the Treatment of Acute Cerebral Infarction,JCYJ20180302173504891)Science and Innovation Commission of Shenzhen(lncRNA Malat1 Mediates SDF1/CXCR4 Axis in Cerebral Angiogenesis after Acute Cerebral Infarction and the Intervention Mechanism of Hydroxysafflor Yellow A,JCYJ 20190812161807600)。
文摘OBJECTIVE:To evaluate the anti-apoptotic efficacy of Qingnao Yizhi formula(清脑益智方,QNYZ)in cultured cerebral cortical neuronal cells(CNCs)and the regulation of the NogoA-Nogo receptor(NgR)/Rho-Rho kinase(ROCK)signaling pathway.METHODS:Primary cultured CNCs were randomly divided into the following groups:normal control group(N-C),hypoxia-reoxygenation group(H/R),high-dose QNYZ group(Q-H),low-dose QNYZ group(Q-L)butylphthalide(NBP)group,and Y-27632(a selective ROCK transduction pathway inhibiter)group.Except those in the N-C group,CNCs were placed in hypoxic conditions for 24 h and then in reoxygenation conditions for 24 h.Cell media was changed every 48 h,and various assays were performed on the 7 th day.Cell viability was evaluated by measuring mitochondrial dehydrogenase activity,using a CCK-8 assay,in triplicate.Synapsin(SYN)protein concentrations were evaluated by enzyme-linked immunosorbent assay.NogoA and RhoA protein expression were evaluated through Western blotting.The gene expression of NogoA,NgR,RhoA,and ROCK was evaluated by reverse transcription-polymerase chain reaction.Cell apoptosis was measured using a terminal deoxynucleotidyl transferase biotin-d UTP nick end labeling assay.RESULTS:Compared with the N-C group,the cell viability of the H/R group decreased significantly(P<0.05).The cell viability values for the Q-H and Q-L groups increased compared with that for the H/R group,and the difference was significant for the Q-H group(P<0.05).The NogoA and RhoA protein levels and the NogoA,NgR,RhoA,and ROCK m RNA expression levels increased in the H/R group,compared with the N-C group,and decreased significantly in the Q-H and Q-L groups(P<0.05)and in the Y-27632 group(P<0.05)compared with the H/R group.The SYN levels in the Q-H,Q-L,and NBP groups significantly increased compared with that in the H/R group(P<0.05).Compared with the H/R group,the numbers of apoptotic cells in the Q-H,Q-L,and NBP groups significantly decreased(P<0.05).CONCLUSION:The presented study demonstrated that QNYZ exerted anti-apoptotic effects on H/R-induced CNCs,possibly through the modulation of the NogoA-NgR/Rho-ROCK signaling pathway and the promotion of synaptic plasticity in H/R CNCs.
基金supported by the National Natural Science Foundation of China,No.81070729the Natural Science Foundation of Hunan Province in China,No.10JJ4023the Hunan Provincial Innovation Foundation for Postgraduate in China,No.CX2011B047
文摘Various retinal injuries induced by ocular hypertension have been shown to induce plastic changes in retinal synapses, but the potential regulatory mechanism of synaptic plasticity after retinal injury was still unclear. A rat model of acute ocular hypertension was established by injecting saline intravitreally for an hour, and elevating the intraocular pressure to 14.63 kPa （110 mmHg）. Western blot assay and immunofluorescence results showed that synaptophysin expression had a distinct spatiotemporal change that increased in the inner plexiform layer within 1 day and spread across the outer plexiform layer after 3 days. Glial fibrillary acidic protein expression in retinae was greatly increased after 3 days, and reached a peak at 7 days, which was also consistent with the peak time of synaptophysin expression in the outer plexiform layer following the increased intraocular pressure. Fluorocitrate, a glial metabolic inhibitor, was intravitreally injected to inhibit glial cell activation following high intraocular pressure. This significantly inhibited the enhanced glial fibrillary acidic protein expression induced by high intraocular pressure injury. Synaptophysin expression also decreased in the inner plexiform layer within a day and the widened distribution in the outer plexiform layer had disappeared by 3 days. The results suggested that retinal glial cell activation might play an important role in the process of retinal synaptic plasticity induced by acute high intraocular pressure through affecting the expression and distribution of synaptic functional proteins, such as synaptophysin.
基金Supported by National Key R&D Program of China(No.2018YFC2001400)Special Research Topic of Health Care(No.13BJZ53+1 种基金No.18BJZ34)Beijing Municipal Science and Technology Commission(No.Z191100004419006)。
文摘AIM:To investigate whether head and neck proprioception and motor control could be compensatory enhanced by long-term vision loss or impairment.METHODS:Individuals who were blind,low vision or sighted were included in the study,which would undergo the head repositioning test(HRT).The constant error(CE),absolute error(AE),variable error(VE)and root mean square error(RMSE)of each subject were statistically analyzed.Data were analyzed using the SAS 9.4.Tukey-Kramer for one-way ANOVA was used for comparison of blind,low vision,and sighted subjects,as well as to compare subjects with balanced vision,strong vision in the left eye and strong vision in the right eye.Independent sample t-test was used to compare subjects with congenital blindness and acquired blindness,as well as left and right hand dominance subjects.RESULTS:A total of 90 individuals(25 blind subjects,31 low vision subjects,and 34 sighted subjects)were included in the study.Among the blind subjects,14 cases had congenital blindness and 11 cases had acquired blindness.Among the blind and low vision subjects,21 cases had balanced binocular vision,17 cases had strong vision in the left eye and 18 cases had strong vision in the right eye.Among all subjects,11 cases were left hand dominance,and 79 cases were right hand dominance.There were significant differences in AE,VE,and RMSE in head rotation between blind,low vision,and sighted subjects(P<0.01),in AE,VE,and RMSE between blind and sighted(P<0.01),and in VE and RMSE between low vision and sighted(P<0.05).No significant difference between blind and low vision(P>0.05).Significant differences in CE and AE of head right rotation and CE of general head rotation between congenital and acquired(P<0.05).No significant differences between left and right hand dominance and in balance or not of binocular vision(P>0.05).CONCLUSION:Long-term vision loss or impairment does not lead to compensatory enhancement of head and neck proprioception and motor control.Acquired experience contributes to HRT performance in the blind and has long-lasting effects on plasticity in the development of proprioception and sensorimotor control.
基金Supported by the National Natural Science Foundation of China:the Mechanism of Shenzhiling in Early Intervention on AD via Functional Brain Circuit PI3K/Akt-MTOR Pathway(No.81573927)the Scientific Research and Graduate Training Project of Beijing Municipal Commission of Education(2016)Young Teachers Project of Beijing University of Chinese Medicine(2019-BUCMXJKY018)。
文摘OBJECTIVE:To investigate the efficacy of Jinsiwei(a patented Chinese herbal compound)on learning and memory impairment,the number of synapses and synaptic plasticity-related structural and functional protein expression in mice with sporadic Alzheimer’s disease(SAD)induced by streptozotocin.METHODS:Seventy-five C57/BL6J male mice were intracerebroventricularly injected with streptozotocin to establish the animal model of SAD.Mice were randomly divided into the model group(MG),donepezil group(DG),and the Jinsiwei high,medium,and low-dose groups(JH,JM,JL).Another fifteen C57/BL6J male mice were injected with artificial cerebrospinal fluid as the control group(CG).The intervention groups were intragastrically administrated with corresponding medicine,while the CG and MG were given 0.5%carboxymethyl cellulose by gavage.After 3 months,the Morris Water Maze test and step-down passive avoidance test were used to assess the learning and memory ability of mice.Synapses in hippocampal CA1 were observed by transmission electron microscope.Immunohistochemistry and western blotting were used to assess the distribution and expression levels of synaptic plasticity-related structural and functional proteins involving drebrin,cofilin,synapsin(syn),and N-methyl D-aspartate receptor subtype 2B(NR2B).RESULTS:The Morris Water Maze results showed that the escape latency in the Jinsiwei intervention groups was significantly shorter than that of the MG.Results of the step-down passive-avoidance test showed that the error times in the Jinsiwei intervention groups were significantly reduced compared with the MG.Transmission electron microscope results showed that the number of synapses in hippocampal CA1 was obviously increased in the Jinsiwei intervention groups compared with the MG.Immunohistochemical and western blotting results revealed that the positive cells and expression levels of drebrin,syn,and NR2B were significantly decreased in the MG and meanwhile cofilin significantly increased,while these changes were reversed after the Jinsiwei treatment.CONCLUSIONS:Jinsiwei can alleviate learning and memory impairments in a mouse model of SAD,increase the number of synapses and enhance synaptic plasticity via rescuing the expression of drebrin,syn,and NR2B and inhibiting cofilin expression.
基金funded by Ministry of Education,University and Research(MIUR)ex-60% research fund University of Brescia,Italy
文摘Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.
基金supported in part by awards from the National Institutes of Health–National Center for Medical Rehabilitation Research(R01HD084645R01HD082109)
文摘The systemic health benefits of regular skeletal muscle activity are well documented.Increased skeletal muscle activity is associated with an improved systemic metabolic state,reduced incidence of diabetes and obesity,and improved function with age.Despite these known systemic benefits,many healthy people do not meet the recommended daily dose of skeletal muscle activity（exercise）needed to prevent systemic metabolic disease,leading to an in-creased prevalence of obesity.
基金supported by the National Natural Science Foundation of China,Nos.81971309 (to CY),32170980 (to CY),82260272 (to DL)the Natural Science Foundation of Jiangxi Province,No.20192BAB205078 (to DL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.2022B1515020012 (to CY)Shenzhen Fundamental Research Program,Nos.JCYJ20210324123212035 (to CY),RCYX202007141 14644167 (to CY),ZDSYS20220606100801003 (to CY)。
文摘Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.
基金Natural Science Foundation-funded Project:Study on the Mechanism of Tuina and Tuina in Regulating the Synaptic Plasticity of Spinal Dorsal Horn in Lumbar Disc Herniation Based on LncRNA-HOTAIR/miR-219 Mediated NMDAR Pathway(No.82174523)Natural Science Foundation of Fujian Province:Study on the Mechanism of Tuina Regulating the Synaptic Plasticity of Spinal Dorsal Horn in Lumbar Disc Herniation based on NMDAR-CAMK2-CREB Pathway(No.2020J01757)+2 种基金Study on Analgesic Mechanism of Tuina on Neuropathic Pain in Spinal Dorsal Horn/ACC Brain Region based on PKA-NMDA-NR2B Pathway(No.2020J01758)Fujian Health Science and Technology Program:Study on the Analgesic Mechanism of Tuina Manipulation On Lumbar Disc Herniation from the Efficacy of miR-219/NR2B Mediated Synaptic Transmission(No.2020GGA070)Effects of Tuina Point Press on AMPA/NMDA Receptor Scaffold Protein and Synaptic Plasticity in Spinal Dorsal Horn of Rats with Neuropathic Pain(No.2020CXA052)。
文摘OBJECTIVE:To investigate whether the Chinese massage system,Tuina,exerts analgesic effects in a rat model of chronic constriction injury(CCI)by remodeling the synaptic structure in the spinal cord dorsal horn(SCDH).METHODS:Sixty-nine male Sprague–Dawley rats were randomly and evenly divided into the normal group,sham group,CCI group,CCI+Tuina group,CCI+MK-801[an N-methyl D-aspartate receptor subtype 2B(NR2B)antagonist]group,and CCI+MK-801+Tuina group.The neuropathic pain model was established using CCI with right sciatic nerve ligation.Tuina was administered 4 d after CCI surgery,using pressing manipulation for 10 min,once daily.Motor function was observed with the inclined plate test,and pain behaviors were observed by the Von Frey test and acetone spray test.At 19 d after surgery,the L3-L5 spinal cord segments were removed.Glutamate,interleukin 1β(IL-1β),and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of NR2B and postsynaptic density protein-95(PSD-95)were detected by Western blot,and the synaptic structure was observed by transmission electron microscopy(TEM).RESULTS:CCI reduced motor function and caused mechanical and cold allodynia in rats,increased glutamate concentration and TNF-αand IL-1βlevels,and increased expression of synapse-related proteins NR2B and PSD-95 in the SCDH.TEM revealed that the synaptic structure of SCDH neurons was altered.Most of these disease-induced changes were reversed by Tuina and intrathecal injection of MK-801(P<0.05 or<0.01).For the majority of experiments,no significant differences were found between the CCI+MK-801 and CCI+MK-801+Tuina groups.CONCLUSIONS:Chinese Tuina can alleviate pain by remodeling the synaptic structure,and NR2B and PSD-95 receptors in the SCDH may be among its targets.
基金“973”Program of the Ministry of Science and Technology of China:Research on Acupoint Optimization,Combination and Evaluation Methods(No.2014CB543103)the SelfSelected Research Program from of China Academy of Chinese Medical Sciences:Study on the Mechanism of Central Amygdala Nucleus Mediated Electroacupuncture on Relieving Chronic Pain and Related Aversive Mood(No.ZZ13-YQ-063)。
文摘OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB and BDNF/TrkB signaling,as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.METHODS:Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine(PCPA)once daily for 2 d.EA was applied at Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),or Shenmen(HT7)+Baihui(GV20)+Sanyinjiao(SP6)(combined)for 30 min daily for 4 d.Spatial learning and memory function was evaluated by the Morris water maze(MWM)test.Protein expressions of hippocampal cAMP-dependent protein kinase(PKA)-Cβ,phosphorylated cAMP-responsive element-binding protein(p-CREB),brainderived neurotrophic factor(BDNF),and tyrosine kinase receptor B(TrkB)were evaluated by Western blotting.Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay.Endogenous neurogenesis was examined with bromodeoxyuridine staining.The MWM test and hippocampal p-CREB,BDNF,and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor(H89).RESULTS:Spatial learning and memory were significantly impaired in rats with insomnia.The spatial learning deficits were ameliorated in the Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),and combined groups;this improvement was significantly greater in the combined group than the single acupoint groups.The spatial memory impairment was improved in the combined,Baihui(GV20),and Shenmen(HT7)groups,but not the Sanyinjiao(SP6)group.The expressions of PKA-Cβ,p-CREB,BDNF,and TrkB were decreased in rats with insomnia.All these proteins were significantly upregulated in the combined group.PKA/p-CREB protein levels were elevated in the Baihui(GV20)and Shenmen(HT7)groups,whereas BDNF/TrkB expression was upregulated in the Sanyinjiao(SP6)group.The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group,whereas the single acupoint groups only showed decreased numbers of apoptotic cells.In the combined group,the PKA inhibitor reversed the improvement of spatial memory and upregulation of pCREB expression caused by EA,but did not affect its activation of BDNF/TrkB signaling.CONCLUSIONS:EA at the single acupoints Baihui(GV20),Shenmen(HT7),or Sanyinjiao(SP6)had an ameliorating effect on the spatial learning and memory deficits induced by insomnia.EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling,facilitating neurogenesis,and inhibiting neuronal apoptosis.These findings indicate that EA at combined acupoints[(Baihui(GV20),Shenmen(HT7),and Sanyinjiao(SP6)]achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints,which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.
