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Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang Department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National Center for Neurological Disorders ShanghaiChina Shanghai key laboratory of brain Function Restoration and neural Regeneration ShanghaiChina State key laboratory of Medical Neurobiology and MOE Frontiers Center for brain science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

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neural Regeneration Research 2025年第10期20卷 2923-2937页

作者： Yan Li Peng Hao Hongmei Duan Fei Hao Wen Zhao Yudan Gao Zhaoyang Yang Kwok-Fai So Xiaoguang Li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina China Rehabilitation science Institute China Rehabilitation Research CenterBeijing Key Laboratory of Neural Injury and RehabilitationBeijingChina Center of neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Beijing key laboratory for Biomaterials and neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Guangdong-HongKong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland laboratory(Guangzhou Regenerative Medicine and Health Guangdong laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State key laboratory of brain and Cognitive sciences The University of Hong KongHong Kong Special Administration RegionChina Center for brain science and brain-Inspired Intelligence Guangdong-HongKong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after ***,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains *** this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic *** findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated ***,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain *** findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

关键词： adult endogenous neurogenesis basic fibroblast growth factor-hyaluronic acid collagen gel cortical remodeling functional recovery migration motor cortex injury neural circuits neural stem cells newborn neurons proliferation

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

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neural Regeneration Research 2025年第10期20卷 2807-2822页

作者： Xizi Song Ruixin Li Xiaolei Chu Qi Li Ruihua Li Qingwen Li Kai-Yu Tong Xiaosong Gu Dong Ming Academy of Medical engineering and Translational Medicine Tianjin UniversityTianjinChina Haihe laboratory of brain-Machine Interface and Human-Machine Fusion TianjinChina Department of Rehabilitation Tianjin University Tianjin HospitalTianjinChina Department of Hand Microsurgery Tianjin University Tianjin HospitalTianjinChina School of Exercise and Health Tianjin University of SportTianjinChina Department of Biomedical engineering the Chinese University of Hong KongHong Kong Special Administrative RegionChina

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and *** on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target *** has led to restrictions on current therapeutic *** this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target *** peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal *** nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury *** damage to target organs can occur,including skeletal muscle atrophy and sensory receptor *** then provide a brief review of the research advances in therapeutic approaches to peripheral nerve *** main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical ***,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ ***,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

关键词： central nervous system central peripheral target organ multilevel pathological analysis nerve regeneration peripheral nerve injury peripheral nervous system target organs therapeutic approach

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen brain science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

Toward understanding the role of genomic repeat elements in neurodegenerative diseases

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neural Regeneration Research 2025年第3期20卷 646-659页

作者： Zhengyu An Aidi Jiang Jingqi Chen Institute of science and Technology for brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers Center for brain science Fudan UniversityShanghaiChina MOE key laboratory of Computational Neuroscience and brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation Center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National key laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

Passive activity enhances residual control ability in patients with complete spinal cord injury

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neural Regeneration Research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng Rao Guiyun Song Wei Song Xiaoguang Li Beijing key laboratory for Biomaterials and neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Rehabilitation Evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State key laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina Department of Rehabilitation engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically *** findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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neural Regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen key laboratory of Neuroimmunomodulation for Neurological Diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS key laboratory of brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial key laboratory of brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of sciences BeijingChina Faculty of Life and Health sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter