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Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

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Neural Regeneration research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun Guangxi Key Laboratory of brain and Cognitive Neuroscience Guilin Medical University department of Genetic Disease research Osaka Metropolitan University Graduate School of Medicine department of Scientific research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,*** works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s *** intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent ***,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical ***,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in *** the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent *** findings indicate strong cross-talk between the two proteins in physiology and *** this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

Using microglia-derived extracellular vesicles to capture diversity of microglial activation phenotypes following neurological injury

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Neural Regeneration research 2024年第8期19卷 1633-1634页

作者： Austyn D.Roseborough Nikita Ollen-Bittle Shawn NWhitehead Vulnerable brain Laboratory Department of Anatomy&Cell BiologySchulich School of Medicine&DentistryLondonOHCanada

Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and *** microglia are unique among brain cells due to their hematologic origin and perform immune function... 详细信息

关键词： neurological cytes activation

Advancing brain-inspired computing with hybrid neural networks

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National Science Review 2024年第5期11卷 56-71页

作者： Faqiang Liu Hao Zheng Songchen Ma Weihao Zhang Xue Liu Yansong Chua Luping Shi Rong Zhao Center for brain-Inspired Computing research Optical Memory National Engineering Research CenterTsinghua University-China Electronics Technology HIK Group Co.Joint Research Center for Brain-inspired ComputingIDGMc Govern Institute for Brain Research Department of Precision Instrument Tsinghua University Neuromorphic Computing Laboratory China Nanhu Academy of Electronics and Information Technology

brain-inspired computing, drawing inspiration from the fundamental structure and information-processing mechanisms of the human brain, has gained significant momentum in recent years. It has emerged as a research paradigm centered on brain–computer dual-driven and multi-network integration. One noteworthy instance of this paradigm is the hybrid neural network(HNN), which integrates computer-science-oriented artificial neural networks(ANNs) with neuroscience-oriented spiking neural networks(SNNs). HNNs exhibit distinct advantages in various intelligent tasks, including perception, cognition and learning. This paper presents a comprehensive review of HNNs with an emphasis on their origin, concepts, biological perspective, construction framework and supporting systems. Furthermore, insights and suggestions for potential research directions are provided aiming to propel the advancement of the HNN paradigm.

关键词： brain-inspired computing hybrid neural network dual-brain driven multi-network integration neuromorphic system

How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University department of Computer Sciences Tsinghua University College of Life Sciences Nankai University Chinese Institute for brain research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(Life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-Hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen department of anatomy and K.K.Leung brain research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier research Center of brain&brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China department of anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li department of Rehabilitation Medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

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Neuroscience Bulletin 2024年第4期40卷 439-450页

作者： Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang department of Neurosurgery of Second Affiliated Hospital and School of brain Science and brain Medicine Key Laboratory for Biomedical Engineering of Education MinistryZhejiang University School of MedicineHangzhou310058China Nanhu brain-computer Interface Institute Hangzhou311100China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain Machine IntegrationKey Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain ***,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was *** showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm *** synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and *** results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

关键词： Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity

Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan department of Medical Imaging AnatomyRadboud University Medical CenterDonders Institute for BrainCognition&BehaviorCenter for Medical NeurosciencePreclinical Imaging Center PRIMERadboud Alzheimer CenterNijmegenthe Netherlands

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the *** at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of *** signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease *** pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier ***,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel ***,the purpose of this review is to provide a new foundation in the study of small vessel disease ***,we discuss the main structural domains and functions of the blood-brain ***,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel ***,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

APE1 regulates mitochondrial DNA damage repair after experimental subarachnoid haemorrhage in vivo and in vitro

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Stroke & Vascular Neurology 2024年第3期9卷 230-242,I0133-I0209页

作者： Kun Dai Zongqi Wang Bixi Gao Longyuan Li Feng Gu Xinyu Tao Wanchun You Zhong Wang department of Neurosurgery&brain and Nerve research Laboratory First Affiliated Hospital of Soochow UniversitySuzhouJiangsuChina Institute of Stroke research Soochow UniversitySuzhouJiangsuChina

Background Subarachnoid haemorrhage(SAH)can result in a highly unfavourable *** recent years,the study of SAH has focused on early brain injury(EBI),which is a crucial progress that contributes to adverse *** can lead to various complications,including mitochondrial dysfunction and DNA ***/apyrimidinic endonuclease 1(APE1)is an essential protein with multifaceted functionality integral to DNA repair and redox ***,the role of APE1 in mitochondrial DNA damage repair after SAH is still *** Our study involved an in vivo endovascular perforation model in rats and an in vitro neuron oxyhaemoglobin ***,the effects of APE1 on mitochondrial DNA damage repair were analysed by western blot,immunofluorescence,quantitative real-time PCR,mitochondrial bioenergetics measurement and neurobehavioural *** We found that the level of APE1 decreased while the mitochondria DNA damage and neuronal death increased in a rat model of *** of APE1 improved short-term and long-term behavioural impairment in rats after *** vitro,after primary neurons exposed to oxyhaemoglobin,APE1 expression significantly decreased along with increased mitochondrial DNA damage,a reduction in the subunit of respiratory chain complex levels and subsequent respiratory chain *** of APE1 relieved energy metabolism disorders in the mitochondrial of neurons and reduced neuronal *** In conclusion,APE1 is involved in EBI after SAH by affecting mitochondrial apoptosis via the mitochondrial respiratory ***1 may potentially play a vital role in the EBI stage after SAH,making it a critical target for treatment.

关键词： APE1 damage vivo after