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Standardized Operational Protocol for Human brain Banking in China

Neuroscience Bulletin 2019年第2期35卷 270-276页

作者： Wenying Qiu Hanlin Zhang Aimin Bao Keqing Zhu Yue Huang Xiaoxin Yan Jing Zhang Chunjiu Zhong Yong Shen Jiangning Zhou Xiaoying Zheng Liwei Zhang Yousheng Shu Beisha Tang Zhenxin Zhang Gang Wang Ren Zhou Bing Sun Changlin Gong Shumin Duan Chao Ma department of Human Anatomy Histology and EmbryologyInstitute of Basic Medical SciencesNeuroscience CenterChinese Academy of Medical SciencesPeking Union Medical College department of neurobiology Zhejiang University School of Medicine neurology Center Beijing Tiantan Hospital Affiliated to Beijing Capital Medical University and Central Brain BankNational Clinical Research Centre for Neurological Disorders department of Human Anatomy and neurobiology Xiangya School of MedicineCentral South University department of Pathology Peking University Health Science Centre department of neurology Zhongshan HospitalFudan University school of Life sciences University of Science and Technology of China Asia-Pacific Economic Cooperation Health science Acad-emy/Institute of Population Research Peking University Beijing Tian Tan hospital Capital Medical University Institute of brain and Cognitive sciences Beijing Normal University Xiangya hospital Central South University department of neurology Peking Union Medical College Hospital department of neurology and Neuroscience Institute Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine department of Pathology Zhejiang University School of Medicine China brain Bank Zhejiang University School of Medicine

With the progress of society, there is an increasing need to tackle disorders of the central nervous system. Human brain tissue, unlike animal tissues, is an irreplaceable resource for the study of neurological diseases (1)Aimed at scientific research and education, the roles of human brain tissue repositories are to acquire brain tissue from donors, prepare, process, and preserve collected samples,provide tissue to specific eligible facilities, and determine the characteristics of each tissue sample.

关键词： Standardized brain Banking increasing

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Antinociceptive effects of novel epibatidine analogs through activation of α4β2 nicotinic receptors

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science China(Life sciences) 2018年第6期61卷 688-695页

作者： Weiwei Li Jingyi Cai Benjamin H Wang Lanting Huang Jing Fan Yun Wang Institutes of brain science and State Key Laboratory of Medical neurobiology Collaborative innovation Center for Brain Science Zhongshan Hospital Fudan University Shanghai 200032 China department of Anesthesiology Shanghai Changzheng Hospital Second Military Medical University Shanghai 200003China east shanghai high school shanghai high school international division

The study of α4β2 nicotinic receptors has provided new indications in the treatment of pain. Efforts have been made to explore new α4β2 nicotinic receptor agonists, including TC-2559, as antinociceptive drugs. In this study, we discovered a set of novel epibatidine analogs with strong binding affinities to the α4β2 nicotinic receptors. Among these compounds, C-159, C-163, and C-9515 attenuated formalin-induced nociceptive responses in mice; C-9515 caused the most potent analgesic effect, which was blocked by mecamylamine, a non-selective nicotinic receptor antagonist. Furthermore, C-9515 potently inhibited chronic constriction injury(CCI)-induced neuropathic pain in rats, which was sensitive to DHβE, a selective α4β2 subtype antagonist,indicating that its analgesic effect was mediated by the activation of the α4β2 nicotinic receptors. In conclusion, the epibatidine analog C-9515 was found to be a potent α4β2 nicotinic receptor agonist with potent analgesic function, which demonstrated potential for the further exploration of its druggability.

关键词： α4β2 nicotinic receptor pain formalin test chronic constriction injury

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GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo/reperfusion rat

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2005年第4期6卷 254-258页

作者：刘建仁丁美萍魏尔清罗建红宋英黄鉴政葛求富胡华朱丽君 department of neurology department of Pharmacology department of neurobiology School of Medicine Zhejiang University Hangzhou 310009 China department of Neurosurgery Second Affiliated Hospital School of MedicineZhejiang University Hangzhou 310009 China

Objective: To determine the protective effect of monosialoganglionside (GM1) and evaluate the influence of GM1 on expression of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in Sprague-Dawley (SD) rats with focal cerebral ische- mia-reperfusion (I/R). Methods: Left middle cerebral artery (MCA) was occluded by an intraluminal suture for 1 h and the brain was reperfused for 72 h in SD rats when infarct volume was measured, GM1 (10 mg/kg) was given ip (intraperitoneally) at 5 min (group A), 1 h (group B) and 2 h (group C) after MCA occlusion (MCAo). Expression of NMDAR1 was detected by Western blot at various time after reperfusion (4 h, 6 h, 24 h, 48 h and 72 h) in ischemic hemispheres of the rats with or without GM1 admin- istered. Results: (1) Adjusted relative infarct volumes of groups A and B were significantly smaller than that of group C and the control group (P<0.01 and P<0.05, respectively). (2) Expression level of NMDAR1 was temporally high at 6 h after reperfusion, and dipped below the normal level at 72 h after reperfusion. GM1 at 5 min after MCAo significantly suppressed the expression of NMDAR1 at 6 h after reperfusion (P<0.05 vs the control). At 72 h after reperfusion, the NMDAR1 expression level of rats treated with GM1 administered (at 5 min or 2 h after MCAo) was significantly higher than that of the control (P<0.05). Conclusion: GM1 can time-dependently reduce infarct volume in rats with focal cerebral I/R partly through stabilizing the expression of NMDAR1.

关键词： G(M1) ganglioside Middle cerebral artery occlusion Reperfusion N-methyl-D-aspartate receptors Rats

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The Pathology of Primary Familial brain Calcification:Implications for Treatment

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Neuroscience Bulletin 2023年第4期39卷 659-674页

作者： Xuan Xu Hao Sun Junyu Luo Xuewen Cheng Wenqi Lv Wei Luo Wan-Jin Chen Zhi-Qi Xiong Jing-Yu Liu Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai200031China College of Life science and Technology Huazhong University of Science and TechnologyWuhan430074China department of neurology and Institute of neurology of First affiliated hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhou350005China department of neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China

Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ataxia,parkinsonism,dementia,depression,headaches,and ***,the etiology of PFBC is largely unknown,and no specific prevention or treatment is *** the past 10 years,six causative genes(SLC20A2,PDGFRB,PDGFB,XPR1,MYORG,and JAM2)have been identified in *** this review,considering mechanistic studies of these genes at the cellular level and in animals,we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC *** systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics,provides a summary of the known composition of brain calcification,and identifies some potential therapeutic targets for PFBC.

关键词： Primary familial brain calcification Causative gene Pathogenesis Preventive and therapeutic strategy

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Autophagy is involved in oral rAAV/Aβ vaccine-induced Aβ clearance in APP/PS1 transgenic mice

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Neuroscience Bulletin 2015年第4期31卷 491-504页

作者： He-Cheng Wang Tao Zhang Bolati Kuerban Ying-Lan Jin Weidong Le Hideo Hara Dong-Sheng Fan Yan-Jiang Wang Takeshi Tabira De-Hua Chui Neuroscience Research Institute & department of neurobiology School of Basic Medical SciencesPeking University Health Science Center Center for Translational Research of neurology Disease First Affiliated HospitalDalian Medical University Division of neurology Department of Internal MedicineSaga University Faculty of Medicine department of neurology Peking University Third Hospital department of neurology Daping HospitalThird Military Medical University department of neurology Graduate School of MedicineJuntendo University

The imbalance between β-amyloid （Aβ） generation and clearance plays a fundamental role in the pathogenesis of Alzheimer＇s disease （AD）. The sporadic form of AD is characterized by an overall impairment in Aβ clearance. Immunotherapy targeting Aβ clearance is believed to be a promising approach and is under active clinical investigation. Autophagy is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aβ clearance. We previously reported that oral vaccination with a recombinant AAV/Aβ vaccine increased the clearance of Aβ from the brain and improved cognitive ability in AD animal models, while the underlying mechanisms were not well understood. In this study, we first demonstrated that oral vaccination with rAAV/Aβ decreased the p62 level and up-regulated the LC3B- II/LC3B-I ratio in APP/PS1 mouse brain, suggesting enhanced autophagy. Further, inhibition of the Akt/mTOR pathway may account for autophagy enhancement. We also found increased anti-Aβ antibodies in the sera of APP/PS1 mice with oral vaccination, accompanied by elevation of complement factors C1q and C3 levels in the brain. Our results indicate that autophagy is closely involved in oral vaccination-induced Aβ clearance, and modulating the autophagy pathway may be an important strategy for AD prevention and intervention.

关键词： oral vaccination autophagy Akt/mTOR pathway Aβ clearance Alzheimer's disease

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Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson’s disease

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Translational Neurodegeneration 2023年第1期12卷 90-110页

作者： Wenying Xu Jie Wang Xin-Ni Li Jingxue Liang Lu Song Yi Wu Zhenguo Liu Bomin Sun Wei-Guang Li department of Rehabilitation medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China department of Neurosurgery Center for Functional NeurosurgeryRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China department of neurology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Deep brain stimulation(DBS)is a well-established and effective treatment for patients with advanced Parkinson’s disease(PD),yet its underlying mechanisms remain ***,primarily conducted in animal models,provides a unique approach that allows cell type-and projection-specific modulation that mirrors the frequency-dependent stimulus effects of ***-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD ***-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs,frequency-dependent synaptic depression,and the intrinsic excitability of postsynaptic *** orchestration leads to conversion of firing patterns,enabling both antidromic and orthodromic modulation of neural *** these mechanisms is vital for decoding position-and programming-dependent effects of ***,patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic *** on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation *** technologies,such as adaptive DBS or directional electrodes,can also be integrated for circuit-specific *** insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

关键词： Parkinson’s disease Deep brain stimulation Optogenetics Opto-DBS Synaptic adaptation Orthodromic effects Antidromic effects Long-lasting therapeutic effects

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A Deep Mesencephalic Nucleus Circuit Regulates Licking Behavior

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Neuroscience Bulletin 2022年第6期38卷 565-575页

作者： Di Zheng Jja-Yu Fu Meng-Yu Tang iao-Dan Yu Yi Zhu Chen Jie Shen Chun-Yue Li Shi-Ze Xiel Shan Lin Minmin Luo Xiao-Ming Li department of neurobiology and department of neurology of Second Affliated HospitalZhejiang University School of MedicineHangzhou 310058China NHC and CAMS Key Laboratory of Medical neurobiology MOE Frontier Science Center for Brain Research and Brainmachine IntegrationSchool of Brain Science and Brian MedicineZhejiang UniversityHangzhou 310058China National Institute of Biological sciences(NIBS) Bejing 102206China Chinese Institute for brain Research Beijing 102206China school of Life sciences Tsinghua UniversityBejing 100084China Center for brain science and brain-Inspired Intelligence Research Units for Emotion and Emotion DisordersChinese Academy of Medical SciencesChina/Guangdong-Hong Kong-Macao Greater Bay AreaJoint Institute for Genetics and Genome Medicine Between Zhejiang University and University of TorontoHangzhou 310058.China

Licking behavior is important for water *** deep mesencephalic nucleus(DpMe)has been implicated in instinctive ***,whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains ***,we found that the activity of the DpMe decreased during water *** of vesicular glutamate transporter 2-positive(VGLUT2+)neurons in the DpMe resulted in increased water ***-expressing(SST+),but not protein kinase C-expressing(PKC-8+),GABAergic neurons in the central amygdala(CeA)preferentially innervated DpMe VGLUT2+*** SST+neurons in the CeA projecting to the DpMe were activated at the onset of licking *** of these CeA SST+GABAergic neurons,but not PKC-8+GABAergic neurons,projecting to the DpMe was sufficient to induce licking behavior and promote water *** findings redefine the roles of the DpMe and reveal a novel CeAssT_DpMevcLUT?cireuit that regulaes icking behavior and promotes water intake.

关键词： Midbrain Amygdala Licking Neural Circuit Optogenetics

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cFos-ANAB:A cFos-based Web Tool for Exploring Activated Neurons and Associated Behaviors

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Neuroscience Bulletin 2021年第10期37卷 1441-1453页

作者： Fan Wang Wenjie Sun Lei Chang Kefang Sun Leying Hou Linna Qian Chaoyin Jin Jiandong Chen Jiali Pu Panmeng Ye Shuang Qiu Jianhong Luo Shumin Duan Baorong Zhang Zhihua Gao Xiaojun Hu Center for Neuroscience and department of neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Medical Information Center Zhejiang University School of MedicineHangzhou 310058China department of neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Hangzhou Hikvision Digital Technology Co. LtdHangzhou 310053China

cFos is one of the most widely-studied genes in the field of ***,there is no systematic database focusing on cFos in *** developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice,comprising 398 brain nuclei and sub-nuclei,and five associated behaviors:pain,fear,feeding,aggression,and sexual *** relationships among behaviors and nuclei(even cell types)under specific stimulating conditions were constructed based on cFos expression profiles extracted from original ***,overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized,leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown *** the analysis function of cFos-ANAB,multi-layered pictures of networks and their relationships can quickly be explored depending on users’*** features provide a useful tool and good reference for early exploration in *** cFos-ANAB database is available at ***.

关键词： cFos expression Curated database brain nucleus Behavior Stimulus Visualization tools

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Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

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Neural Regeneration Research 2023年第5期18卷 1154-1160页

作者： Ting Shen Jia-Li Pu Ya-Si Jiang Yu-Mei Yue Ting-Ting He Bo-Yi Qu Shuai Zhao Ya-Ping Yan Hsin-Yi Lai Bao-Rong Zhang department of neurology of the second affiliated hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of neurology of the second affiliated hospital Interdisciplinary Institute of Neuroscience and TechnologyKey Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouZhejiang ProvinceChina department of neurology of Sir Run Run Shaw hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina College of Biomedical Engineering and Instrument science Key Laboratory for Biomedical Engineering of Ministry of EducationZhejiang UniversityHangzhouZhejiang ProvinceChina

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors

关键词： cognition imaging genetics magnetic resonance imaging multi-modality Parkinson’s disease polygenic risk score single nucleotide polymorphism ultra-high field

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Effect of Apolipoprotein E Genotypes on Huntington’s Disease Phenotypes in a Han Chinese Population

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Neuroscience Bulletin 2019年第4期35卷 756-762页

作者： Xiao-Yan Li Yan-Bin Zhang Miao Xu Hong-Rong Cheng Yi Dong Wang Ni Hong-Lei Li Zhi-Ying Wu department of neurology and Research Center of neurology in the second affiliated hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310009 China department of neurology and Institute of neurology First Affiliated Hospital Fujian Medical University Fuzhou 350005 China department of neurology and Institute of neurology Huashan Hospital Shanghai Medical College Fudan University Shanghai 200041 China Joint Institute for Genetics and Genome medicine between Zhejiang University and University of Toronto Zhejiang University Hangzhou 310009 China

Huntington's disease(HD)is an autosomal dominant degenerative disease that mainly encompasses movement,cognition,and behavioral *** apolipoprotein E(APOE)gene is thought to be associated with many neurodegenerative ***,we enrolled a cohort of 223 unrelated Han Chinese patients with HD and1241 unrelated healthy controls in Southeastern China and analyzed the correlation between APOE genotypes and HD *** results showed that the frequency of the E4 allele(7.1%)in HD patients was statistically less than that in controls(12.0%)(P =0.004).In addition,we divided patients into motor-onset and non-motor-onset groups,and analyzed the relationship with APOE *** results,however,were ***,the age at onset(AAO),defined as the age at the onset of motor symptoms,was compared in each APOE genotype subgroup and multivariate regression analysis was used to exclude the interference of CAG repeat length on AAO,but no association was found between APOE genotypes and ***,we analyzed adult-onset HD to exclude the interference caused by juvenile HD(n = 13),and the results were ***,our study suggests that APOE may not be a genetic modifier for HD,especially for adult-onset HD among Chinese of Han *** the best of our knowledge,this is the first study of the correlation between APOE genotypes and HD phenotypes in a Han Chinese population.

关键词： Huntington's disease Phenotype Apolipoprotein E Han Chinese population

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