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Lysosomal Hydrolase Cathepsin D Non-proteolytically Modulates Dendritic Morphology in Drosophila

Neuroscience Bulletin 2020年第10期36卷 1147-1157页

作者： Ting Zhang Daxiao Cheng Cunjin Wu Xingyue Wang Qiang Ke Huifang Lou Liya Zhu Xiao-Dong Wang shumin duan Yi-Jun Liu Department of Neurobiology Key Laboratory of Medical Neurobiology of the Ministry of Health of ChinaZhejiang Province Key Laboratory of NeurobiologyZhejiang University School of MedicineHangzhou 310058China Department of Diagnostics Hangzhou Normal University Medical SchoolHangzhou 311121China Department of Laboratory Medicine Hangzhou Normal University Affiliated HospitalHangzhou 310015China Department of Psychiatry Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Mental Health Center Zhejiang University School of MedicineHangzhou 310058China

The main lysosomal protease cathepsin D(cathD)is essential for maintaining tissue homeostasis via its degradative function,and its loss leads to ceroid accumulation in the mammalian nervous system,which results in progressive neurodegeneration.Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis,cell proliferation,and migration.Along these lines,we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function.Upon cathD depletion,class I and class III arborization(da)neurons in Drosophila larvae exhibited aberrant dendritic morphology,including overbranching,aberrant turning,and elongation defects.Reintroduction of wild-type cathD or its proteolyticallyinactive mutant dramatically abolished these morphological defects.Moreover,cathD knockdown also led to dendritic defects in the adult mushroom bodies,suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems.Taken together,our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.

关键词： Cathepsin D Dendritic arborization Sensory neuron Mushroom body Actin Drosophila

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Brain-wide Mapping of Mono-synaptic Afferents to Different Cell Types in the Laterodorsal Tegmentum

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Neuroscience Bulletin 2019年第5期35卷 781-790页

作者： Xiaomeng Wang Hongbin Yang Libiao Pan Sijia Hao Xiaotong Wu Li Zhan Yijun Liu Fan Meng Huifang Lou Ying Shen shumin duan Hao Wang Department of Neurobiology and Department of Neurosurgery of The Second Affiliated Hospital Key Laboratory of Medical Neurobiology of the Ministry of Health of ChinaNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine

The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear.Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex(VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive(PV?) GABAergic cells received preferential projections from local LDT neurons.With regard to the different subtypes of GABAergic cells, aconsiderable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatinpositive cells than to PV?cells. Diverse inputs to the LDT on a system-wide level were revealed.

关键词： Laterodorsal tegmentum Rabies virus retrograde tracing Limbic lobe Mice

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FTO is a transcriptional repressor to auto-regulate its own gene and potentially associated with homeostasis of body weight

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Journal of Molecular Cell Biology 2019年第2期11卷 118-132页

作者： Shu-Jing Liu Hui-Ling Tang Qian He Ping Lu Tao Fu Xu-Ling Xu Tao Su Mei-Mei Gao shumin duan Yan Luo Yue-Sheng Long Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260 China School of Basic Medical Sciences Zhejiang University Hangzhou 310058 China Institute of Neuroscience Zhejiang University School of MedicineHangzhou 310058 China

Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe^2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m^6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood. Here we show that ketogenic diet-derived ketone body β-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells. Interestingly, the FTO protein represses Fto promoter activity, which can be offset by BHB. We then demonstrate that FTO binds to its own gene promoter, and Fe^2+, but not 2-OG, impedes this binding and increases FTO expression. The BHB-induced occupancy of the promoter by FTO influences the assembly of the basal transcriptional machinery. Importantly, a loss-of-function FTO mutant (I367F), which induces a lean phenotype in FTO^I367F mice, exhibits augmented binding and elevated potency to repress the promoter. Furthermore, FTO fails to bind to its own promoter that promotes FTO expression in the hypothalamus of high-fat diet-induced obese and 48-h fasting mice, suggesting a disruption of the stable expression of this gene. Taken together, this study uncovers a new function of FTO as a Fe^(2+)-sensitive transcriptional repressor dictating its own gene switch to form an auto-regulatory loop that may link with the hypothalamic control of body weight.

关键词： FTO transcriptional repressor hypothalamus ferrous ion obesity

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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 neuroscience.Currently,there is no systematic database focusing on cFos in neuroscience.We 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 behavior.Direct relationships among behaviors and nuclei(even cell types)under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications.Moreover,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 circuits.Using the analysis function of cFos-ANAB,multi-layered pictures of networks and their relationships can quickly be explored depending on users’purposes.These features provide a useful tool and good reference for early exploration in neuroscience.The cFos-ANAB database is available at ***.

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

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Neuroscience Bulletin calls for papers

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Neuroscience Bulletin 2013年第4期 520-520页

作者： shumin duan Editorial Office of Neuroscience Bulletin

关键词： Neuroscience Bulletin calls for papers link

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Neuroscience Bulletin calls for papers

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Neuroscience Bulletin 2013年第1期29卷 I0007-I0007页

作者： shumin duan Editorial Offce of Neuroscience Bulletin

关键词： Neuroscience Bulletin calls for papers link

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Neuroscience Bulletin calls for papers

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Neuroscience Bulletin 2014年第4期 717-717页

作者： shumin duan

关键词： Neuroscience Bulletin calls for papers

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Neuroscience Bulletin calls for papers

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Neuroscience Bulletin 2014年第3期 541-541页

作者： shumin duan Editorial Office of Neuroscience Bulletin

关键词： Neuroscience Bulletin calls for papers

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Neuroscience Bulletin calls for papers

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Neuroscience Bulletin 2013年第6期 8-8页

作者： shumin duan Editorial Office of Neuroscience Bulletin

Neuroscience Bulletin is an international bimonthly journal in neuroscience,and is the official journal of the Chinese Neuroscience Society.Beginning with the first 2009 issue,Neuroscience Bulletin is included in the Science Citation Index Expanded(SCI-E,available as the Web of Science),Neuroscience Citation Index,Biological Abstracts,and Biosis Previews databases.It is also indexed/abstracted by Medline/PubMed,Chemical Abstracts,Index Medicus,Excerpta Medica,SCOPUS,IndexCopernicus,Chinese Science Citation Database(CSCD)

关键词： Neuroscience Bulletin calls for papers

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Neuroscience Bulletin calls for papers

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Neuroscience Bulletin 2013年第5期 674-674页

作者： shumin duan

Neuroscience Bulletin is an international bimonthly journal in neuroscience,and is the official journal of the Chinese Society for Neuroscience.Beginning with the first 2009 issue,Neuroscience Bulletin is included in the Science Citation Index Expanded(SCI-E,available as the Web of Science),Neuroscience Citation Index,Biological Abstracts,and Biosis Previews databases.It is also indexed/abstracted by Medline/PubMed,Chemical Abstracts,Index Medicus,Excerpta Medica,SCOPUS,IndexCopernicus,Chinese Science Citation Database(CSCD),Chinese National Knowledge Infrastructure(CNKI)and Wanfang database.According to 2012 Journal Citation Reports,

关键词： Neuroscience Bulletin calls for papers

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