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Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

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Neural Regeneration Research 2024年第10期19卷 2111-2112页

作者： Dominique Ebedes Cesar V.Borlongan University of South Florida Morsani College of Medicine TampaFLUSA Center of Excellence for Aging and brain Repair Department of Neurosurgery and Brain RepairUniversity of South Florida Morsani College of MedicineTampaFLUSA

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the united States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

关键词： straight pathology pathogenesis

Traumatic brain injury treatment using a rodent model of homelessness

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Neural Regeneration Research 2024年第9期19卷 1873-1874页

作者： Molly Monsour Cesar V.Borlongan University of South Florida Morsani College of Medicine TampaFLUSA Center of Excellence for Aging and brain Repair Department of Neurosurgery and Brain RepairUniversity of South Florida Morsani College of MedicineTampaFLUSA

Introduction:Traumatic brain injury(TBI)is a common diagnosis among veterans secondary to combat experiences.TBI is also rampant among those experiencing homelessness,possibly due to veterans making up 12.3%of the homeless population(Tsai and Rosenheck,2015),or due to the high risk of violence or trauma among those experiencing homelessness.TBI is up to 10×more prevalent among those experiencing homelessness(Stubbs et al.,2020;Dell et al.,2021).

关键词： diagnosis TBI less

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1291-1298页

作者： Qi Jia Jin Li Xiaofeng Guo Yi Li You Wu Yuliang Peng Zongping Fang Xijing Zhang Department of Anesthesiology and Perioperative Medicine and Department of Intensive Care unit Xijing Hospital The Fourth Military Medical University Department of Critical Care Medicine Translational Research Institute of brain and brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins. Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis, while providing nutrients and support for cell survival. Chaperone-mediated autophagy activity can be detected in almost all cells, including neurons. Owing to the extreme sensitivity of neurons to their environmental changes, maintaining neuronal homeostasis is critical for neuronal growth and survival. Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases. It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction. Under certain conditions, regulation of chaperone-mediated autophagy activity attenuates neurotoxicity. In this paper, we review the changes in chaperone-mediated autophagy in neurodegenerative diseases, brain injury, glioma, and autoimmune diseases. We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

关键词： chaperone-mediated autophagy neurodegenerative disease neuronal homeostasis neuroprotection

The Neural Mechanism of Knowledge Assembly in the Human brain Inspires Artificial Intelligence Algorithm

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Neuroscience Bulletin 2024年第2期40卷 280-282页

作者： Xiang Ji Wentao Jiang Xiaoru Zhang Ming Song Shan Yu Tianzi Jiang University of the Chinese Academy of Sciences Beijing 100049China brainnetome Center Institute of AutomationThe Chinese Academy of SciencesBeijing 100190China Laboratory of brain Atlas and brain-inspired Intelligence Institute of AutomationThe Chinese Academy of SciencesBeijing 100190China CAS Center for Excellence in brain Science and Intelligence Technology The Chinese Academy of SciencesBeijing 100190China Research Center for Augmented Intelligence Zhejiang LabHangzhou 311100China

When new information enters the brain,a human's prior knowledge of the world can change rapidly through a process referred to as"knowledge assembly".Recently,Nelli et al.investigated the neural correlates of knowledge assembly in the human brain using functional MRI.Further,inspired by the neural mechanism,the authors developed an artificial neural network algorithm to permit rapid knowledge assembly,improving the flexibility of the system[1].Once again,this research demonstrates that studying how the brain works can lead to better computational algorithms.

关键词： neural knowledge artificial

State-sensitive convolutional sparse coding for potential biomarker identification in brain signals

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Science China(Information Sciences) 2024年第5期67卷 270-286页

作者： Puli WANG Yu QI Gang PAN College of Computer Science and Technology Zhejiang University State Key Laboratory of brain-Machine Intelligence Zhejiang University MOE Frontier Science Center for brain Science and brain-machine Integration Zhejiang University Affiliated Mental Health Center & Hangzhou Seventh People's Hospital Zhejiang University School of Medicine

The identification of prototypical waveforms, such as sleep spindles and epileptic spikes, is crucial for the diagnosis of neurological disorders. These prototypical waveforms are usually recurrently presented in certain brain states, serving as potential biomarkers for clinical evaluations. Convolutional sparse coding(CSC) approaches have demonstrated strength in identifying recurrent patterns in time-series. However,existing CSC approaches do not explicitly explore state-specific patterns, making it difficult to identify state-related biomarkers. To address this problem, we propose state-sensitive CSC to learn state-specific prototypical waveforms. Specifically, we model signals of a certain state with specific waveforms that only appear frequently in this state and background waveforms that are independent of states. Based on this,state-sensitive CSC separates state-specific waveforms from background ones explicitly by incorporating incoherence constraints into optimizations. Experiments with epilepsy brain signals demonstrate that our approach can effectively identify prototypical waveforms in pre-ictal states, providing potential biomarkers for seizure prediction. Our approach provides a promising tool for automatic biomarker candidate identification.

关键词： convolutional sparse coding prototypical waveforms state-specific dictionary biomarker identification neural signal processing

Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

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National Science Review 2024年第4期11卷 70-83页

作者： Huiying Zhao Jinrong Liu Yujin Shao Xiang Feng Binhan Zhao Li Sun Yijun Liu Linghui Zeng Xiao-ming Li Hongbin Yang Shumin Duan Yan-qin Yu Department of Neurology of Second Affiliated Hospital and School of brain Science and brain Medicine Zhejiang University School of Medicine Nanhu brain-Computer Interface Institute Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-Machine Integration State Key Laboratory of Brain-Machine Intelligence Zhejiang University NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of Medicine Hangzhou City University

The nucleus of Darkschewitsch(ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons(NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot shock.Optogenetic and chemogenetic manipulations revealed that NDGABA neurons mediate freezing behavior.Moreover, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray(l PAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part(Gi V). Together,these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from the l PAG to Gi V, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.

关键词： nucleus of Darkschewitsch GABAergic population defensive behavior freezing neural circuitry

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 unclear.Here,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 disrupted.Immunohistochemistry 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 synapses.Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and density.Our 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

Neural Circuitry Involving Substance P in Male Sexual Behavior

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Neuroscience Bulletin 2024年第4期40卷 544-546页

作者： Xinrong Wang Junqiang Zheng Han Xu Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital and School of brain Science and brain Medicine Zhejiang University School of MedicineHangzhou310058China Nanhu brain-Computer Interface Institute Hangzhou311100China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

Male sexual behavior is an innate social behavior crucial for reproduction[1].Previous studies have identified several brain regions crucial for the control of both sexual and aggressive behaviors in males.Yet,molecularly specified neural circuits that specifically control male sexual behavior remain elusive.Consistent with the inherently rewarding nature of sexual behavior,previous research has implicated the role of the dopamine system in regulating sexual desire[2].However,the interaction between reward and copulation at the circuit level remains largely unexplored.Besides,it is unclear if the associated neural pathways are specific in modulating sexual reward.

关键词： behavior neural specified

Interplay between the glymphatic system and neurotoxic proteins in Parkinson’s disease and related disorders:current knowledge and future directions

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Neural Regeneration Research 2024年第9期19卷 1973-1980页

作者： Yumei Yue Xiaodan Zhang Wen Lv Hsin-Yi Lai Ting Shen Department of Neurology of Sir Run Run Shaw Hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Emergency Medicine The University of Hong KongHong Kong Special Administrative RegionChina Department of Neurology of the Second Affiliated Hospital and School of brain Science and brain Medicine Interdisciplinary Institute of Neuroscience and TechnologyKey Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouZhejiang ProvinceChina College of Biomedical Engineering and Instrument Science Zhejiang UniversityHangzhouZhejiang ProvinceChina MOE Frontier Science Center for brain Science and brain-Machine Integration State Key Laboratory of Brain-machine IntelligenceSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina

Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

关键词： atypical parkinsonism glymphatic system magnetic resonance imaging neurotoxic proteins Parkinson’s disease