Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Alt...Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.展开更多
Objective:To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats,and to explore its mechanism of action.Methods:The global cerebral ischemia-reperfu...Objective:To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats,and to explore its mechanism of action.Methods:The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats.Rats were intraperitoneally injected with puerarin(100 mg/kg) 1 h before ischemia and once every 6 h afterwards.The learning-memory ability was evaluated by the passive avoidance test.Th...展开更多
INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depres...INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.展开更多
Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention a...Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.Methods In this hospital-based retrospective study,we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders(schizophrenia,depressive episode,bipolar disorder,pervasive developmental disorder,and unspecified mood disorder)that accounted for the overall proportion of patients admitted.The rank and proportion of these mental disorders,demographic characteristics and disease indicators were analysed.Results There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years,with a sharp decline in 2020 due to the COVID-19 pandemic,followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022.The average age of hospitalization decreased significantly from 20.7 to 16.2 years,with a marked increase in the 12-17-year-old age group.The proportion of female hospitalizations increased from 39.2%to 55.2%,with a corresponding decrease in male hospitalizations.There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.Conclusion This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.展开更多
Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarke...Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.展开更多
During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increase...During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National In...Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.展开更多
A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lew...A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lewy bodies(DLB),multiple system atrophy(MSA),corticobasal syndrome(CBS),and progressive supranuclear palsy(PSP).These disorders are differentiated neuropathologically by their dominant protein pathologies involvingα-synuclein(α-syn)and/or tau,the types of brain cells affected,such as neurons,oligodendroglia,and astrocytes,and the specific brain regions involved(Tolosa et al.,2021).展开更多
BACKGROUND Bipolar disorder(BD)is a severe mental illness characterized by significant mood swings.Effective drug treatment modalities are crucial for managing BD.AIM To analyze the current status and future trends of...BACKGROUND Bipolar disorder(BD)is a severe mental illness characterized by significant mood swings.Effective drug treatment modalities are crucial for managing BD.AIM To analyze the current status and future trends of global research on BD drug treatment over the last decade.METHODS The Web of Science Core Collection database spanning from 2015 to 2024 was utilized to retrieve literature related to BD drug treatment.A total of 2624 articles were extracted.Data visualization and analysis were conducted using CiteSpace,VOSviewer,Pajek,Scimago Graphica,and R-studio bibliometrix to identify RESULTS The United States,China,and the United Kingdom have made the most significant contributions to research on BD drug treatment and formed notable research collaboration networks.The University of Pittsburgh,Massachusetts General Hospital,and the University of Michigan have been identified as the major research institutions in this field.The Journal of Affective Disorders is the most influential journal.A keyword analysis revealed research hotspots related to clinical symptoms,drug efficacy,and genetic mechanisms.A citation analysis identified the management guidelines published by Yatham et al in 2018 as the most cited paper.CONCLUSION This study provides a detailed overview of the field of BD drug treatment,highlighting key contributors,research hotspots,and future directions.The study findings can be employed as a reference for future research and policymaking,which may enable further development and optimization of BD pharmacotherapy.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
Objective To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021.Methods Using data from the Global Burden of Disease Study(GBD)2021,the number of prevalent cases,preva...Objective To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021.Methods Using data from the Global Burden of Disease Study(GBD)2021,the number of prevalent cases,prevalence rate,disability-adjusted life years(DALYs),and age-standardized DALY rates were analyzed by sex,age group,and province for headache disorders and their subtypes(migraine and tension-type headache[TTH])between 1990 and 2021.Percentage changes during this period were also estimated.Results In 2021,approximately 426 million individuals in China were affected by headache disorders,with an age-standardized prevalence rate of 27,582.61/100,000.The age-standardized DALY rate for all headache disorders was 487.15/100,000.Between 1990 and 2021,the number of prevalent cases increased by 37.78%,while the prevalence of all headache disorders,migraine,and TTH increased by 6.92%,7.57%,and 7.86%,respectively.The highest prevalence was observed in the 30-34 age group(39,520.60/100,000).Migraine accounted for a larger proportion of DALYs attributable to headache disorders,whereas TTH has a greater impact on its prevalence.In 2021,the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang(617.85/100,000)and Shanghai(542.86/100,000).Conclusion The prevalence of headache disorders is increasing in China.Effective health education,improve diagnosis and treatment are essential,particularly for middle-aged working populations and women of childbearing age.展开更多
Traditional Chinese medicine(TCM)has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder.However,its widespread application has been hindered by th...Traditional Chinese medicine(TCM)has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder.However,its widespread application has been hindered by the unclear biological essence of TCM syndromes and therapeutic mechanisms.As an emerging interdisciplinary field,phenomics integrates multi-dimensional data including genome,transcriptome,proteome,metabolome,and microbiome.When combined with TCM's holistic philosophy,it forms TCM phenomics,providing novel approaches to reveal the biological connotation of TCM syndromes and the mechanisms of herbal medicine.Taking glycolipid metabolism disorder as an example,this paper explores the application of TCM phenomics in glycolipid metabolism disorder.By analyzing molecular characteristics of related syndromes,TCM phenomics identifies differentially expressed genes,metabolites,and gut microbiota biomarkers to elucidate the dynamic evolution patterns of syndromes.Simultaneously,it deciphers the multi-target regulatory networks of herbal formulas,demonstrating their therapeutic effects through mechanisms including modulation of insulin signaling pathways,improvement of gut microbiota imbalance,and suppression of inflammatory responses.Current challenges include the subjective nature of syndrome diagnosis,insufficient standardization of animal models,and lack of integrated multi-omics analysis.Future research should employ machine learning,multimodal data integration,and cross-omics longitudinal studies to establish quantitative diagnostic systems for syndromes,promote the integration of precision medicine in TCM and western medicine,and accelerate the modernization of TCM.展开更多
This article comprehensively explores the relationship between anxiety and hypertensive disorders of pregnancy(HDP),covering epidemiology,potential mechanisms,and management strategies.HDP is the second leading cause ...This article comprehensively explores the relationship between anxiety and hypertensive disorders of pregnancy(HDP),covering epidemiology,potential mechanisms,and management strategies.HDP is the second leading cause of maternal and perinatal morbidity and mortality,encompassing subtypes such as gestational hypertension,preeclampsia,and eclampsia.Research indicates that anxiety is closely associated with the occurrence of HDP,potentially influencing blood pressure regulation and vascular function through neuroendocrine,inflammatory,genetic,and gut microbiota effects.Epidemiological data show that anxiety is prevalent during pregnancy and is linked to an increased risk of HDP.Biological mechanism studies reveal that anxiety can increase the risk of HDP by activating the hypothalamic-pituitary-adrenal axis,promoting inflammation,and affecting gut microbiota.In terms of treatment and management,psychological interventions(such as relaxation training,yoga,and mindfulness meditation)and pharmacological treatments(such as labetalol and nifedipine)play important roles in alleviating anxiety and improving the prognosis of HDP.Additionally,multidisciplinary collaboration and long-term postpartum follow-up are crucial for reducing the long-term risk of cardiovascular diseases.Despite significant progress in research on anxiety and HDP,many issues still require further exploration,including in-depth mechanism studies,optimization of clinical interventions,improvement of multidisciplinary collaboration models,long-term follow-up studies,and the impact of cultural and social factors.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
BACKGROUND Functional gastrointestinal disorders(FGIDs)in children present with chronic symptoms like abdominal pain,diarrhea,and constipation without identifiable structural abnormalities.These disorders are closely ...BACKGROUND Functional gastrointestinal disorders(FGIDs)in children present with chronic symptoms like abdominal pain,diarrhea,and constipation without identifiable structural abnormalities.These disorders are closely linked to gut-brain axis dysfunction,altered gut microbiota,and psychosocial stress,leading to psychia-tric comorbidities such as anxiety,depression,and behavioral issues.Under-standing this bidirectional relationship is crucial for developing effective,holistic management strategies that address physical and mental health.AIM To examine the psychiatric impacts of FGIDs in children,focusing on anxiety and depression and their association with other neurodevelopmental disorders of childhood,such as attention-deficit/hyperactivity disorder,emphasizing the role of the gut-brain axis,emotional dysregulation,and psychosocial stress.Key mechanisms explored include neurotransmitter dysregulation,microbiota imbalance,central sensitization,heightening stress reactivity,emotional dysregulation,and symptom perception.The review also evaluates the role of family dynamics and coping strategies in exacerbating FGID symptoms and contributing to psychiatric conditions.METHODS A narrative review was conducted using 328 studies sourced from PubMed,Scopus,and Google Scholar,covering research published over the past 20 years.Inclusion criteria focused on studies examining FGID diagnosis,gut-brain mechanisms,psychiatric comorbidities,and psychosocial factors in pediatric populations.FGIDs commonly affecting children,including functional constipation,abdominal pain,irritable bowel syndrome,gastroesophageal reflux,and cyclic vomiting syndrome,were analyzed concerning their psychological impacts.RESULTS The review highlights a strong connection between FGIDs and psychiatric symptoms,mediated by gut-brain axis dysfunction,dysregulated microbiota,and central sensitization.These physiological disruptions increase children’s vulnerability to anxiety and depression,while psychosocial factors-such as chronic stress,early-life trauma,maladaptive family dynamics,and ineffective coping strategies-intensify the cycle of gastrointestinal and emotional distress.CONCLUSION Effective management of FGIDs requires a biopsychosocial approach integrating medical,psychological,and dietary interventions.Parental education,early intervention,and multidisciplinary care coordination are critical in mitigating long-term psychological impacts and improving both gastrointestinal and mental health outcomes in children with FGIDs.展开更多
文摘Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
基金Supported by the Key Technologies Research and Development Program of Shaanxi Province(No.2002k10-G2)
文摘Objective:To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats,and to explore its mechanism of action.Methods:The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats.Rats were intraperitoneally injected with puerarin(100 mg/kg) 1 h before ischemia and once every 6 h afterwards.The learning-memory ability was evaluated by the passive avoidance test.Th...
基金funded by the Construction Project of the"Flagship"Department of Chinese and Western Medicine Coordination(LiuL/2024-221)the 2024 Medical Service and Security Capacity Improvement Project(National Clinical Key Specialty Construction)(LiuL/Huwei Medical/2024-65)+5 种基金the Shanghai Traditional Chinese Medicine Standardization Project(LiuL/No.2023JSP03)the Shanghai Key Discipline Construction Project of Traditional Chinese Medicine(Clinical)(LiuL/2024-No.3)the Shanghai Technical Standardization Management and Promotion Project(LiuL/No.SHDC22023212)the Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project(2022)(LiuL/No.2022Cx004)Clinical research project of Shanghai Health Commission-Youth Project(LW/No.20214Y0056)Shanghai Institute of Traditional Chinese Medicine for Mental Health(LW/No.SZB2023201).
文摘INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.
文摘Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.Methods In this hospital-based retrospective study,we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders(schizophrenia,depressive episode,bipolar disorder,pervasive developmental disorder,and unspecified mood disorder)that accounted for the overall proportion of patients admitted.The rank and proportion of these mental disorders,demographic characteristics and disease indicators were analysed.Results There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years,with a sharp decline in 2020 due to the COVID-19 pandemic,followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022.The average age of hospitalization decreased significantly from 20.7 to 16.2 years,with a marked increase in the 12-17-year-old age group.The proportion of female hospitalizations increased from 39.2%to 55.2%,with a corresponding decrease in male hospitalizations.There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.Conclusion This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.
文摘Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
基金supported by the National Institute of Environmental Health Sciences(R21ES035492,R21ES035969)National Institutes of Child Health(R01HD090214)(to PA).
文摘During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
文摘Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.
文摘A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lewy bodies(DLB),multiple system atrophy(MSA),corticobasal syndrome(CBS),and progressive supranuclear palsy(PSP).These disorders are differentiated neuropathologically by their dominant protein pathologies involvingα-synuclein(α-syn)and/or tau,the types of brain cells affected,such as neurons,oligodendroglia,and astrocytes,and the specific brain regions involved(Tolosa et al.,2021).
基金Supported by the National College Students’Innovative Entrepreneurial Training Plan Program,No.202410403067the Innovation and Entrepreneurship Training Program for College Students in Jiangxi Province,No.S202410403035.
文摘BACKGROUND Bipolar disorder(BD)is a severe mental illness characterized by significant mood swings.Effective drug treatment modalities are crucial for managing BD.AIM To analyze the current status and future trends of global research on BD drug treatment over the last decade.METHODS The Web of Science Core Collection database spanning from 2015 to 2024 was utilized to retrieve literature related to BD drug treatment.A total of 2624 articles were extracted.Data visualization and analysis were conducted using CiteSpace,VOSviewer,Pajek,Scimago Graphica,and R-studio bibliometrix to identify RESULTS The United States,China,and the United Kingdom have made the most significant contributions to research on BD drug treatment and formed notable research collaboration networks.The University of Pittsburgh,Massachusetts General Hospital,and the University of Michigan have been identified as the major research institutions in this field.The Journal of Affective Disorders is the most influential journal.A keyword analysis revealed research hotspots related to clinical symptoms,drug efficacy,and genetic mechanisms.A citation analysis identified the management guidelines published by Yatham et al in 2018 as the most cited paper.CONCLUSION This study provides a detailed overview of the field of BD drug treatment,highlighting key contributors,research hotspots,and future directions.The study findings can be employed as a reference for future research and policymaking,which may enable further development and optimization of BD pharmacotherapy.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
基金supported by the National Key Research and Development Program of China(2018YFC1315301).
文摘Objective To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021.Methods Using data from the Global Burden of Disease Study(GBD)2021,the number of prevalent cases,prevalence rate,disability-adjusted life years(DALYs),and age-standardized DALY rates were analyzed by sex,age group,and province for headache disorders and their subtypes(migraine and tension-type headache[TTH])between 1990 and 2021.Percentage changes during this period were also estimated.Results In 2021,approximately 426 million individuals in China were affected by headache disorders,with an age-standardized prevalence rate of 27,582.61/100,000.The age-standardized DALY rate for all headache disorders was 487.15/100,000.Between 1990 and 2021,the number of prevalent cases increased by 37.78%,while the prevalence of all headache disorders,migraine,and TTH increased by 6.92%,7.57%,and 7.86%,respectively.The highest prevalence was observed in the 30-34 age group(39,520.60/100,000).Migraine accounted for a larger proportion of DALYs attributable to headache disorders,whereas TTH has a greater impact on its prevalence.In 2021,the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang(617.85/100,000)and Shanghai(542.86/100,000).Conclusion The prevalence of headache disorders is increasing in China.Effective health education,improve diagnosis and treatment are essential,particularly for middle-aged working populations and women of childbearing age.
基金National Natural Science Foundation of China(82474323)High Level Chinese Medical Hospital Promotion Project(HLCMHPP20230CZ40907)China Academy of Chinese Medical Sciences Outstanding Young Scientific and Technological Talents Program(ZZ13-YQ-026).
文摘Traditional Chinese medicine(TCM)has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder.However,its widespread application has been hindered by the unclear biological essence of TCM syndromes and therapeutic mechanisms.As an emerging interdisciplinary field,phenomics integrates multi-dimensional data including genome,transcriptome,proteome,metabolome,and microbiome.When combined with TCM's holistic philosophy,it forms TCM phenomics,providing novel approaches to reveal the biological connotation of TCM syndromes and the mechanisms of herbal medicine.Taking glycolipid metabolism disorder as an example,this paper explores the application of TCM phenomics in glycolipid metabolism disorder.By analyzing molecular characteristics of related syndromes,TCM phenomics identifies differentially expressed genes,metabolites,and gut microbiota biomarkers to elucidate the dynamic evolution patterns of syndromes.Simultaneously,it deciphers the multi-target regulatory networks of herbal formulas,demonstrating their therapeutic effects through mechanisms including modulation of insulin signaling pathways,improvement of gut microbiota imbalance,and suppression of inflammatory responses.Current challenges include the subjective nature of syndrome diagnosis,insufficient standardization of animal models,and lack of integrated multi-omics analysis.Future research should employ machine learning,multimodal data integration,and cross-omics longitudinal studies to establish quantitative diagnostic systems for syndromes,promote the integration of precision medicine in TCM and western medicine,and accelerate the modernization of TCM.
文摘This article comprehensively explores the relationship between anxiety and hypertensive disorders of pregnancy(HDP),covering epidemiology,potential mechanisms,and management strategies.HDP is the second leading cause of maternal and perinatal morbidity and mortality,encompassing subtypes such as gestational hypertension,preeclampsia,and eclampsia.Research indicates that anxiety is closely associated with the occurrence of HDP,potentially influencing blood pressure regulation and vascular function through neuroendocrine,inflammatory,genetic,and gut microbiota effects.Epidemiological data show that anxiety is prevalent during pregnancy and is linked to an increased risk of HDP.Biological mechanism studies reveal that anxiety can increase the risk of HDP by activating the hypothalamic-pituitary-adrenal axis,promoting inflammation,and affecting gut microbiota.In terms of treatment and management,psychological interventions(such as relaxation training,yoga,and mindfulness meditation)and pharmacological treatments(such as labetalol and nifedipine)play important roles in alleviating anxiety and improving the prognosis of HDP.Additionally,multidisciplinary collaboration and long-term postpartum follow-up are crucial for reducing the long-term risk of cardiovascular diseases.Despite significant progress in research on anxiety and HDP,many issues still require further exploration,including in-depth mechanism studies,optimization of clinical interventions,improvement of multidisciplinary collaboration models,long-term follow-up studies,and the impact of cultural and social factors.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
文摘BACKGROUND Functional gastrointestinal disorders(FGIDs)in children present with chronic symptoms like abdominal pain,diarrhea,and constipation without identifiable structural abnormalities.These disorders are closely linked to gut-brain axis dysfunction,altered gut microbiota,and psychosocial stress,leading to psychia-tric comorbidities such as anxiety,depression,and behavioral issues.Under-standing this bidirectional relationship is crucial for developing effective,holistic management strategies that address physical and mental health.AIM To examine the psychiatric impacts of FGIDs in children,focusing on anxiety and depression and their association with other neurodevelopmental disorders of childhood,such as attention-deficit/hyperactivity disorder,emphasizing the role of the gut-brain axis,emotional dysregulation,and psychosocial stress.Key mechanisms explored include neurotransmitter dysregulation,microbiota imbalance,central sensitization,heightening stress reactivity,emotional dysregulation,and symptom perception.The review also evaluates the role of family dynamics and coping strategies in exacerbating FGID symptoms and contributing to psychiatric conditions.METHODS A narrative review was conducted using 328 studies sourced from PubMed,Scopus,and Google Scholar,covering research published over the past 20 years.Inclusion criteria focused on studies examining FGID diagnosis,gut-brain mechanisms,psychiatric comorbidities,and psychosocial factors in pediatric populations.FGIDs commonly affecting children,including functional constipation,abdominal pain,irritable bowel syndrome,gastroesophageal reflux,and cyclic vomiting syndrome,were analyzed concerning their psychological impacts.RESULTS The review highlights a strong connection between FGIDs and psychiatric symptoms,mediated by gut-brain axis dysfunction,dysregulated microbiota,and central sensitization.These physiological disruptions increase children’s vulnerability to anxiety and depression,while psychosocial factors-such as chronic stress,early-life trauma,maladaptive family dynamics,and ineffective coping strategies-intensify the cycle of gastrointestinal and emotional distress.CONCLUSION Effective management of FGIDs requires a biopsychosocial approach integrating medical,psychological,and dietary interventions.Parental education,early intervention,and multidisciplinary care coordination are critical in mitigating long-term psychological impacts and improving both gastrointestinal and mental health outcomes in children with FGIDs.
