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Altered Retinal Dopamine Levels in a Melatonin-proficient Mouse Model of Form-deprivation Myopia

Neuroscience Bulletin 2022年第9期38卷 992-1006页

作者： Kang-Wei Qian Yun-Yun Li Xiao-Hua Wu Xue Gong Ai-Lin Liu Wen-Hao Chen Zhe Yang Ling-Jie Cui Yun-Feng Liu Yuan-Yuan Ma Chen-Xi Yu Furong Huang Qiongsi Wang Xiangtian Zhou Jia Qu Yong-Mei Zhong Xiong-Li Yang Shi-Jun Weng state key laboratory of medical neurobiology and moe frontiers center for brain science Institutes of Brain ScienceFudan UniversityShanghai200032China Discipline of Neuroscience and Department of Anatomy and Physiology College of Basic Medical SciencesShanghai Jiao Tong University School of MedicineShanghai200025China School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical UniversityWenzhou325027China Department of Immunology School of Basic Medical SciencesAnhui Medical UniversityHefei230032China

Reduced levels of retinal dopamine,a key regulator of eye development,are associated with experimental myopia in various species,but are not seen in the myopic eyes of C57BL/6 mice,which are deficient in melatonin,a neurohormone having extensive interactions with ***,we examined the relationship between form-deprivation myopia(FDM)and retinal dopamine levels in melatonin-proficient CBA/CaJ *** found that these mice exhibited a myopic refractive shift in form-deprived eyes,which was accompanied by altered retinal dopamine *** melatonin receptors were pharmacologically blocked,FDM could still be induced,but its magnitude was reduced,and retinal dopamine levels were no longer altered in FDM animals,indicating that melatonin-related changes in retinal dopamine levels contribute to ***,FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ *** previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.

关键词： Myopia Refractive development Dopamine Melatonin Mouse Retina

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Spatiotemporal coding of natural odors in the olfactory bulb

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2023年第11期24卷 1057-1061页

作者： Mengxue LIU Nan JIANG Yingqian SHI Ping WANG Liujing ZHUANG Biosensor National Special laboratory Key Laboratory for Biomedical Engineering of Education MinistryDepartment of Biomedical EngineeringZhejiang UniversityHangzhou310027China The moe frontier science center for brain science&brain-machine Integration Zhejiang UniversityHangzhou310027China state key laboratory of Transducer Technology Chinese Academy of SciencesShanghai200050China

Smell that exists in the natural environment is composed of numerous odor molecules(Bushdid et al.,2014).The mammalian olfactory system can accurately identify environmental olfactory cues,including those related to f... 详细信息

关键词： emotional coding Spatiotemporal

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Unlimited source of human microglia inspiring physiopathological and translational studies of the central nervous system

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science China(Life sciences) 2022年第8期65卷 1683-1684页

作者： Yuxin Li Bo Peng Department of Neurosurgery Jinshan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceFudan UniversityShanghai 201508China Department of Neurosurgery Huashan HospitalFudan UniversityShanghai 200032China Co-Innovation center of Neuroregeneration Nantong UniversityNantong 226001China

The retinal organoid is a vital model for studying retinal development and related diseases, especially for the human retina(Jin et al., 2019). The retina constitutes an integral part of the central nervous system(CNS... 详细信息

关键词： system translational organo

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A thermodynamic model showing that information recording can drive active ion transport

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2058-2060页

作者： Xiang Zou Kun Song Minbiao Ji Lingzhao Min Liangfu Zhou Ying Mao Liang Chen Department of Neurosurgery Neurosurgical Institute of Fudan UniversityNational Center for Neurological DisordersHuashan HospitalFudan UniversityShanghai200040China Department of Physics Fudan UniversityShanghai200433China state key laboratory of medical neurobiology and moe frontiers center for brain science School of Basic Medical Sciences and Institutes of Brain ScienceFudan UniversityShanghai200040China

Dear Editor,Ion gradients are characteristic features of a living cell that do not represent thermodynamic *** unequilibrium status are maintained by various ion pumps such as Na-K-ATPase,which are known as the P-type *** mechanism of Na-K-ATPase is described as Post-Albers cycle1(Fig.1a).However,the reaction scheme is non-Michaelis-Menten kinetics assembled from transient-state results,which can hardly be used to rebuild the real reaction cycle.

关键词： recording maintained showing

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Inhibiting DNA methylation alleviates cisplatininduced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1305-1321页

作者： Yingzi He Zhiwei Zheng Chang Liu Wen Li Liping Zhao Guohui Nie Huawei Li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China NHC key laboratory of Hearing Medicine(Fudan University) Shanghai 200031China Department of Otolaryngology and Institute of Translational Medicine Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University Health Science CenterShanghai 200032China Institutes of Biomedical sciences Fudan UniversityShanghai 200032China The Institutes of brain science and the Collaborative Innovation center for brain science Fudan UniversityShenzhen 518035China

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing *** study aimed to assess the potential effect of the DNA methyltransferase(DNMT)inhibitor RG108 on cisplatin-induced ***,apoptosis assay,and auditory brainstem response(ABR)were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells(HCs)and spiral ganglion neurons(SGNs).Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential(MMP)*** oxygen species(ROS)amounts were evaluated by Cellrox green and Mitosox-red *** respiratory function evaluation was performed by determining oxygen consumption rates(OCRs).The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs,and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS ***,RG108 upregulated BCL-2 and downregulated APAF1,BAX,and BAD in HEI-OC1 cells,and triggered the PI3K/AKT *** expression of low-density lipoprotein receptor-related protein 1(LRP1)and high methylation of the LRP1 promoter were observed after cisplatin ***108 treatment can increase LRP1expression and decrease LRP1 promoter *** conclusion,RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

关键词： Cisplatin DNMT Apoptosis Hair cell Spiral ganglion neurons RG108 Mitochondrial dysfunction ROS

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Pathological Networks Involving Dysmorphic Neurons in Type ⅡFocal Cortical Dysplasia

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Neuroscience Bulletin 2022年第9期38卷 1007-1024页

作者： Yijie Shao Qianqian Ge Jiachao Yang Mi Wang Yu Zhou Jin-Xin Guo Mengyue Zhu Jiachen Shi Yiqi Hu Li Shen Zhong Chen Xiao-Ming Li Jun-Ming Zhu Jianmin Zhang Shumin Duan Jiadong Chen center for Neuroscience and Department of Neurosurgery of the Second Affiliated Hospital NHC and CAMS Key Laboratory of Medical NeurobiologyMOE Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang University School of MedicineHangzhou310058China Department of Neurosurgery of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou310009China The moe key laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial key laboratory for Cancer Molecular Cell Biology Life Sciences InstituteZhejiang UniversityHangzhou310058China Department of Orthopedic Surgery School of Medicinethe Second Affiliated HospitalZhejiang UniversityHangzhou310009China Hangzhou Innovation center Zhejiang UniversityHangzhou310058China Institute of Pharmacology&Toxicology NHC and CAMS Key Laboratory of Medical NeurobiologyCollege of Pharmaceutical SciencesSchool of Basic Medical SciencesZhejiang UniversityHangzhou310058China key laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province College of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310058China center for Neuroscience and Department of Neurology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou310058China NHC and CAMS key laboratory of medical neurobiology Center for Brain Science and Brain-Inspired IntelligenceJoint Institute for Genetics and Genome Medicine betweenGuangdong Hong Kong Macao Greater Bay AreaZhejiang University and the University of TorontoZhejiang University School of MedicineHangzhou310058China

Focal cortical dysplasia(FCD)is one of the most common causes of drug-resistant *** neurons are the major histopathological feature of typeⅡFCD,but their role in seizure genesis in FCD is *** we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy *** analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in typeⅡFCD,including an enlarged soma,aberrant dendritic arbors,increased current injection for rheobase action potential firing,and reduced action potential firing ***,the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na^(+)-K^(+)-Cl^(−)*** addition,we found a depolarizing shift of the GABA reversal potential in the CamKⅡ-cre::PTENflox/flox mouse model of drug-resistant epilepsy,suggesting that enhanced GABAergic inputs might depolarize dysmorphic ***,imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in typeⅡFCD.

关键词： Focal cortical dysplasia Dysmorphic neuron Whole-cell patch-clamp recording Morphological reconstruction Excitation-inhibition balance

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Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice

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Neuroscience Bulletin 2023年第1期39卷 29-40页

作者： Xiaoke Xie Shangyue Gong Ning Sun Jiazhu Zhu Xiaobin Xu Yongxian Xu Xiaojing Li Zhenhong Du Xuanting Liu Jianmin Zhang Wei Gong Ke Si Department of Psychiatry The First Affiliated HospitalZhejiang University School of MedicineHangzhou310012China College of Biomedical Engineering and Instrument science Zhejiang UniversityHangzhou310012China Intelligent Optics&Photonics Research center Jiaxing Research InstituteZhejiang UniversityJiaxing314001China Department of Neurosurgery of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou310012China moe frontier science center for brain science&brain-Machine Integration NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310012China state key laboratory of Modern Optical Instrumentation College of Optical Science and EngineeringZhejiang UniversityHangzhou310012China

Fear memory contextualization is critical for selecting adaptive behavior to *** fear conditioning(CFC)is a classical model for elucidating related underlying neuronal *** primary visual cortex(V1)is the primary cortical region for contextual visual inputs,but its role in CFC is poorly ***,our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval,and both CFC learning and extinction increased the turnover rate of axonal boutons in *** frequency of neuronal Ca^(2+)activity decreased after CFC learning,while CFC extinction reversed the decrease and raised it to the naïve *** to control mice,the frequency of neuronal Ca^(2+)activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction,indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca^(2+)*** findings reveal a critical role of microglia in neocortical information processing in V1,and suggest potential approaches for cellular-based manipulation of acquired fear memory.

关键词： Contextual fear conditioning Calcium imaging Primary visual cortex Cortical plasticity Microglial depletion Learning and memory

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The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities

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Neuroscience Bulletin 2023年第3期39卷 393-408页

作者： Qiyuan Zhuang Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghai 200040China National center for Neurological Disorders Huashan HospitalFudan UniversityShanghai 200040China Shanghai key laboratory of brain Function Restoration and Neural Regeneration Huashan HospitalFudan UniversityShanghai 200040China Institute for Translational brain Research Fudan UniversityShanghai 200032China state key laboratory of medical neurobiology and moe frontiers center for brain science Institute for Translational Brain ResearchInstitutes of Brain ScienceFudan UniversityShanghai 200032China Neurosurgical Institute of Fudan University Shanghai 200032China

Glioma is the most common and lethal intrinsic primary tumor of the *** controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of *** the components constituting tumors,glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor *** stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor,in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this *** approaches have revealed the tumor-promoting properties of distinct tumor cell states,glial,neural,and immune cell populations in the tumor *** between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to ***,we discuss the heterogeneity and relevant functions of tumor cell state,microglia,monocyte-derived macrophages,and neurons in glioma,highlighting their bilateral effects on ***,we describe potential therapeutic approaches and targets beyond standard treatments.

关键词： Glioma origin Stem/progenitor cell Oncometabolite Immune heterogeneity Neuron-tumor interaction

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Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain

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Zoological Research 2023年第3期44卷 543-555页

作者： Rong-Jun Ni Yi-Yan Wang Tian-Hao Gao Qi-Run Wang Jin-Xue Wei Lian-Sheng Zhao Yang-Rui Ma Xiao-Hong Ma Tao Li Mental Health center and Psychiatric laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical medical Research center for Mental Disorders ChengduSichuan 610044China Golden Apple Jincheng NO.1 Secondary School ChengduSichuan 610213China Affiliated Mental Health center&Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhouZhejiang 310013China NHC and CAMS key laboratory of medical neurobiology MOE Frontier Science Center for Brain Science and Brain-machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310014China Guangdong-Hong Kong-Macao Greater Bay Area center for brain science and brain-Inspired Intelligence GuangzhouGuangdong 510799China

Acute administration of MK-801(dizocilpine),an N-methyl-D-aspartate receptor(NMDAR)antagonist,can establish animal models of psychiatric ***,the roles of microglia and inflammation-related genes in these animal models of psychiatric disorders remain ***,we found rapid elimination of microglia in the prefrontal cortex(PFC)and hippocampus(HPC)of mice following administration of the dual colony-stimulating factor 1 receptor(CSF1R)/c-Kit kinase inhibitor PLX3397(pexidartinib)in drinking *** administration of MK-801 induced hyperactivity in the open-field test(OFT).Importantly,PLX3397-induced depletion of microglia prevented the hyperactivity and schizophrenia-like behaviors induced by ***,neither repopulation of microglia nor inhibition of microglial activation by minocycline affected MK-801-induced ***,microglial density in the PFC and HPC was significantly correlated with behavioral *** addition,common and distinct glutamate-,GABA-,and inflammation-related gene(116 genes)expression patterns were observed in the brains of PLX3397-and/or MK-801-treated ***,10 common inflammation-related genes(CD68,CD163,CD206,TMEM119,CSF3R,CX3CR1,TREM2,CD11b,CSF1R,and F4/80)with very strong correlations were identified in the brain using hierarchical clustering *** correlation analysis demonstrated that the behavioral changes in the OFT were most significantly associated with the expression of inflammation-related genes(NLRP3,CD163,CD206,F4/80,TMEM119,and TMEM176a),but not glutamate-or GABA-related genes in PLX3397-and MK-801-treated ***,our results suggest that microglial depletion via a CSF1R/c-Kit kinase inhibitor can ameliorate the hyperactivity induced by an NMDAR antagonist,which is associated with modulation of immune-related genes in the brain.

关键词： Microglia Psychiatric disorders Prefrontal cortex Hippocampus Immunity Colony-stimulating factor 1 receptor

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Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells

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Neuroscience Bulletin 2019年第4期35卷 673-687页

作者： Ling-Zhu Li Ning Yin Xue-Yan Li Yanying Miao Shuo Cheng Fang Li Guo-Li Zhao Shu-Min Zhong Xin Wang Xiong-Li Yang Zhongfeng Wang Department of Neurology Institutes of Brain Science State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Zhongshan Hospital Fudan University

Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrites and ***,we investigated whether and how Racl modulates synaptic transmission in mouse retinal ganglion cells(RGCs)using selective conditional knockout of Racl(Racl-cKO).Racl-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents,while glycine/GABA_A receptor-mediated miniature inhibitory postsynaptic currents were not *** the total GluA1 protein level was increased in Racl-cKO mice,its expression in the membrane component was *** did not affect spine-like branch density in single dendrites,but significantly reduced the dendritic complexity,which resulted in a decrease in the total number of dendritic spine-like *** results suggest that Racl selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

关键词： Rac1 Retinal ganglion cell Excitatory synaptic transmission Dendrite Dendritic spine

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