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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

Relationship Between Short-chain Fatty Acids and Parkinson’s Disease:A Review from Pathology to Clinic

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Neuroscience Bulletin 2024年第4期40卷 500-516页

作者： Wen-Xiang Duan Fen Wang Jun-Yi Liu Chun-Feng Liu department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhou215004China department of Neurology Dushu Lake Hospital affiliated to Soochow UniversitySuzhou215125China Jiangsu Key Laboratory of neuropsychiatric Diseases and Institute of Neuroscience Soochow UniversitySuzhou215123China

Parkinson’s disease(PD)is a complicated neurodegenerative disease,characterized by the accumulation ofα-synuclein(α-syn)in Lewy bodies and neurites,and massive loss of midbrain dopamine *** evidence suggests that gut microbiota and microbial metabolites are involved in the development of *** these,short-chain fatty acids(SCFAs),the most abundant microbial metabolites,have been proven to play a key role in brain-gut *** this review,we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor *** research should focus on further elucidating the role of SCFAs in neuroinflammation,as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

关键词： Parkinson’s disease Short-chain fatty acids Microbial metabolites Brain-gut-microbiota axis

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

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2024年第9期19卷 2081-2088页

作者： Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng Xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng Chun-Feng Liu department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina department of Neurology Xuzhou Central HospitalXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of neuropsychiatric Disease and Institute of Neuroscience Soochow UniversitySuzhouJiangsu ProvinceChina

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal *** dysfunction can precede the onset of motor symptoms by several *** microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain ***/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease *** this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota *** found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor ***,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with ***,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and *** of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier *** results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s ***,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that c

关键词： C/EBP/AEP signaling pathway endotoxemia fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease

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General Psychiatry 2024年第1期37卷 53-63页

作者： Xingqi Wu Yibing Yan Panpan Hu Lu Wang Yue Wu Pan Wu Zhi Geng Guixian Xiao Shanshan Zhou Gongjun Ji Bensheng Qiu Ling Wei Yanghua Tian Hesheng Liu Kai Wang department of Neurology First ffiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina School of Mental Health and Psychological Sciences Anhui Medical UniversityHefeiAnhuiChina Anhui Province Key Laboratory of Cognition and neuropsychiatric Disorders HefeiAnhuiChina Collaborative Innovation Center of neuropsychiatric Disorders and Mental Health HefeiAnhuiChina department of Psychology and Sleep Medicine The Second Affliated Hospital of Anhui Medical UniversityHefeiAnhuiChina Center for Biomedical Imaging University of Science and Technology of ChinaHefeiAnhuiChina institute of Artificial Intlligence Hefei Comprehensive National Science CenterHefeiAnhuiChina department of Neuroscience Medical University of South CarolinaCharlestonSouth CarolinaUSA

Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for ***,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD *** We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with *** In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every *** included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the *** were evaluated at baseline and after *** longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over *** The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale *** baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at ***,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)*** D

关键词： stimulation Alzheimer maintained

How do lateral septum projections to the ventral CA1 influence sociability?

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Neural Regeneration Research 2024年第8期19卷 1789-1801页

作者： Dan Wang Di Zhao Wentao Wang Fengai Hu Minghu Cui Jing Liu Fantao Meng Cuilan Liu Changyun Qiu Dunjiang Liu Zhicheng Xu Yameng Wang Yu Zhang Wei Li Chen Li department of Rehabilitation Medicine Binzhou Medical University HospitalBinzhouShandong ProvinceChina Medical Research Center Binzhou Medical University HospitalBinzhouShandong ProvinceChina Institute for Metabolic&neuropsychiatric Disorders Binzhou Medical University HospitalBinzhouShandong ProvinceChina department of Psychology Binzhou Medical University HospitalBinzhouShandong ProvinceChina College of Nursing Binzhou Medical UniversityBinzhouShandong ProvinceChina

Social dysfunction is a risk factor for several neuropsychiatric *** studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social *** r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea *** this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence *** res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these ***,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in *** findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty *** findings provide new insights rega rding the neural circuits that regulate sociability.

关键词： chemogenetics GABA receptor GABAergic neurons glutamatergic neurons lateral septum neural excitability neural projection social novelty social preference ventral CA1

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration

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Bone Research 2024年第2期12卷 390-406页

作者： Xinshu Zhang Yao Xiao Bo Hu Yanhao Li Shaoyang Zhang Jian Tian Shuo Wang Zaijin Tao Xinqi Zeng Ning-Ning Liu Baojie Li Shen Liu department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RdShanghai 200233PR China Section of Spine Surgery Department of OrthopaedicsChangzheng HospitalNaval Medical UniversityShanghai 200003PR China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200241PR China department of Orthopaedics Wuxi Ninth People’s Hospital Affiliated to Soochow UniversityWuxi 214062PR China State Key Laboratory of Systems Medicine for Cancer Center for Single-Cell OmicsSchool of Public HealthShanghai Jiao Tong University School of MedicineShanghai 200025China

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe *** are widely recognized as a fibrotic trigger during peritendinous adhesion ***,different clusters of macrophages have various functions and receive multiple regulation,which are both still *** our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon *** transcriptomes of over 74000 human single cells were *** results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion ***,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human ***,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages *** together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their *** results provide potential therapeutic targets against human tendon adhesion.

关键词： tendon analysis landscape

Structure,ligands,and roles of GPR126/ADGRG6 in the development and diseases

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Genes & Diseases 2024年第1期11卷 294-305页

作者： Qi Li Anran Huo Mengqi Li Jiali Wang Qiao Yin Lumiao Chen Xin Chu Yuan Qin Yuwan Qi Yang Li Hengxiang Cui Qifei Cong Institute of Neuroscience and Jiangsu Key Laboratory of neuropsychiatric Diseases Soochow UniversitySuzhouJiangsu215123China department of Neurology and Clinical Research Center of Neurological Disease The Second Affliated Hospital of Soochow UniversitySuzhouJiangsu 215004China department of Nephrology The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China department of Emergency Center The Second Affiliated Hospital of Nantong UniversityNantongJiangsu226001China department of Neurology Huzhou Central HospitalThe Affiliated Huzhou HospitalZhejiang University School of MedicineHuzhouZhejiang 313000China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China

Adhesion G protein-coupled receptors(aGPCRs)are the second largest diverse group within the GPCR superfamily,which play critical roles in many physiological and patho-logical processes through cell-cell and cell-extracellular matrix *** adhesion GPCR Adgrg6,also known as GPR126,is one of the better-characterized ***126 was previously found to have critical developmental roles in Schwann cell maturation and its mediated myelination in the peripheral nervous system in both zebrafish and *** studies have extended our understanding of GPR126-mediated roles during develop-ment and in human *** this review,we highlighted these recent advances in GPR126 in expression profile,molecular structure,ligand-receptor interactions,and associated physiological and pathological functions in development and diseases.

关键词： Adhesion G protein-coupled receptor Function GPR126/Adgrg6 Ligand Structure

MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

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Neural Regeneration Research 2024年第3期19卷 557-562页

作者： Bridget Martinez Philip V.Peplow department of Pharmacology University of Nevada-RenoRenoUSA department of Medicine University of Nevada-RenoRenoUSA department of Anatomy University of OtagoDunedinNew Zealand

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric *** cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not *** diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are *** for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure *** is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be *** expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity *** recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual *** the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood *** studies are warranted with children and adults with attention deficit hyperactivity disorder,and

关键词： adults attention deficit hyperactivity disorder biomarkers blood plasma blood serum children microRNA total white blood cells whole blood