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Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of medical psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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Metaverse for mental health disorders:Opportunities and challenges

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World Journal of Clinical Cases 2025年第4期13卷 8-14页

作者： Subho Chakrabarti department of psychiatry Postgraduate Institute of Medical Education and ResearchChandigarh 160012UTIndia

Several articles on the mental health impact of the metaverse and the need to balance its potential benefits with the risks of metaverse use has recently *** metaverse consists of a combination of immersive technologies and artificial intelligence *** metaverse differs from the preceding digital psychiatric interventions due to its complex structure and interactions between *** diverse functions of the metaverse ensure that it may have a substantial impact on mental ***,the evidence for its efficacy in treating mental health disorders is limited to a few *** mental health benefits of immersive technologies are well-documented and suggest that metaverse-based psychiatric treatment may be similarly *** mental health risks of the metaverse are largely unknown,and it is not clear whether they will be greater than other digital psychiatric *** more research is needed to determine whether metaverse-based psychiatric treatment will meet the standards of appropriate mental healthcare.

关键词： Metaverse Mental health Benefits Risks Challenges

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Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： Laura Huggon Emma L.Clayton UK Dementia Research Institute at King’s College London LondonUK department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly *** and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

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Insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration Research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An M.Voets Tim Vanmierlo Rudy Schreiber BIOMED Biomedical Research Institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium department of psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands University MS Center(UMSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

关键词： academic approval consequences

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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie Hu Panpan Hu Xingqi Wu Kai Wang department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina department of psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and *** Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients *** transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological *** the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and *** has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological ***,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of *** study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated *** review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s *** mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also ***,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity

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Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

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Science China Chemistry 2025年第01期 377-384页

作者： Shiwen Liu Xuerui Wan Meng Zhao Jiaqi Wang Weilan Wu Linlin You Yonggui Yuan Qian Xu Rong Gao Key Laboratory of Environmental Medicine Engineering Ministry of Education School of Public Health Southeast University Key Laboratory of Modern Toxicology of Ministry of Education Department of Hygienic Analysis and Detection School of Public HealthNanjing Medical University department of Psychosomatics and psychiatry Zhongda Hospital School of Medicine Southeast University

The measurement of amino acid and monoamine neurotransmitters（NTs） in serum plays a central role in the identification and monitoring of clinical panic disorder（PD）. However, the strong polarity and chemical heterogeneity of NTs make direct extraction and rapid detection extremely challenging. Herein, we developed a strategy that integrated solid phase extraction based on magnetic Fe3O4coated with polydopamine（Fe3O4@PDA） and direct analysis of mass spectrometry in real time（DART-MS） for quantification of 10 NTs. We systematically investigated the optimal conditions of this strategy to achieve good accuracy and precision. Compared with existing magnetic solid phase extraction methods for NTs detection in biological samples, this strategy could adsorb more targets while having similar adsorption efficiencies, and the total process time was reduced by an average of 69.42%. We rapidly determined the metabolic abnormality of 6 types of NTs in the serum of PD patients and demonstrated their diagnostic accuracy. In addition, an outstanding feature of PD in which tryptophan was more metabolized by the KYN pathway and the 5-hydroxytryptamine pathway was inhibited could be elucidated by this strategy. Our results highlighted the potential ability of Fe3O4@PDA coupled with DART-MS to assist in the clinical diagnosis of PD.

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Decoding molecular mechanisms:brain aging and Alzheimer's disease

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Neural Regeneration Research 2025年第8期20卷 2279-2299页

作者： Mahnoor Hayat Rafay Ali Syed Hammad Qaiser Mohammad Uzair Khalid Al-Regaiey Roaa Khallaf Lubna Abdullah Mohammed Albassam Imdad Kaleem Xueyi Wang Ran Wang Mehwish SBhatti Shahid Bashir Atta-ur-Rahman School of Applied Biosciences(ASAB) National University of Sciences and Technology(NUST)IslamabadPakistan department of Biotechnology Quaid-i-Azam UniversityIslamabadPakistan department of Biological Sciences Faculty of Basic&Applied SciencesInternational Islamic University Islamabad(IIUI)IslamabadPakistan department of Bioengineering King Fahd University of Petroleum and MineralsDhahranSaudi Arabia department of Physiology College of MedicineKing Saud UniversityRiyadhSaudi Arabia department of Neurology Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia department of Mental Health Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia department of Biosciences Commission on Science and Technology for Sustainable Development in the South(COMSATS University)IslamabadPakistan department of psychiatry The First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Mental Health Institute of Hebei medical University ShijiazhuangHebei ProvinceChina department of Neurobiology and Behavior University of CaliforniaIrvineCAUSA Neuroscience Center King Fahad Specialist Hospital DammamDammamSaudi Arabia

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for *** aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's *** these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging *** these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect *** review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

关键词： Alzheimer’s disease brain aging cognitive health dementia molecular mechanisms neuronal activity neuroplasticity neurotransmission

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S Y Yau Kwok-Fai So Li Zhang Haining Ou department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina department of psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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How to construct neuroscience-informed psychiatric classification?Towards nomothetic networks psychiatry

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World Journal of psychiatry 2021年第1期11卷 1-12页

作者： Drozdstoy Stoyanov Michael HJ Maes department of psychiatry and medical psychology Research InstituteMedical University of PlovdivPlovdiv 4000Bulgaria department of psychiatry Deakin UniversityGeelong 3220Australia

psychiatry remains in a permanent state of crisis,which fragmented psychiatry from the field of *** crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic,biological,molecular,pan-omics,precision,cognitive and phenomenological psychiatry,folk psychology,mind-brain dualism,descriptive psychopathology,and *** current“gold standard”Diagnostic and Statistical Manual of Mental Disorders/International Classification of Diseases taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning ***,it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic *** aim of this paper is to explain the new nomothetic network psychiatry(NNP)approach,which uses machine learning methods to build data-driven causal models of mental illness by assembling risk-resilience,adverse outcome pathways(AOP),cognitome,brainome,staging,symptomatome,and phenomenome latent scores in a causal *** latter may be trained,tested and validated with Partial Least Squares *** approach not only allows to compute pathway-phenotypes or biosignatures,but also to construct reliable and replicable nomothetic networks,which are,therefore,generalizable as disease *** integrating the validated feature vectors into a well-fitting nomothetic network,clustering analysis may be applied on the latent variable scores of the R/R,AOP,cognitome,brainome,and phenome latent *** pattern recognition method may expose new(transdiagnostic)classes of patients which if cross-validated in independent samples may constitute new(transdiagnostic)nosological categories.

关键词： psychiatry Major depression Mood disorders Schizophrenia Antioxidants Oxydative stress

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