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DOI | 10.1073/pnas.2001679118 |
Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration | |
Nagy D.; Ennis K.A.; Wei R.; Su S.C.; Hinckley C.A.; Gu R.-F.; Gao B.; Massol R.H.; Ehrenfels C.; Jandreski L.; Thomas A.M.; Nelson A.; Gyoneva S.; Hajós M.; Burkly L.C. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:6 |
英文摘要 | Identifying molecular mediators of neural circuit development and/or function that contribute to circuit dysfunction when aberrantly reengaged in neurological disorders is of high importance. The role of the TWEAK/Fn14 pathway, which was recently reported to be a microglial/neuronal axis mediating synaptic refinement in experience-dependent visual development, has not been explored in synaptic function within the mature central nervous system. By combining electrophysiological and phosphoproteomic approaches, we show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and postsynaptic proteins in adult mouse hippocampal slices. Importantly, this is relevant in two models featuring synaptic deficits. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid-beta-overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/ Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Fn14; Stroke; Synaptic plasticity; Synaptic transmission; TWEAK |
语种 | 英语 |
scopus关键词 | amyloid beta protein; tumor necrosis factor ligand superfamily member 12; tumor necrosis factor receptor superfamily member 12A; animal experiment; animal model; animal tissue; Article; cerebrovascular accident; controlled study; electrophysiology; female; male; mouse; nerve cell plasticity; nerve degeneration; nonhuman; pathophysiology; phosphoproteomics; priority journal; protein phosphorylation; signal transduction; synaptic transmission |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180730 |
作者单位 | Clinical Sciences, Biogen, Cambridge, MA 02142, United States; Biogen Postdoctoral Scientist Program, Cellular Physiology, Biogen, Cambridge, MA 02142, United States; Genetic and Neurodevelopmental Disease Research, Biogen, Cambridge, MA 02142, United States; Chemical Biology and Proteomics, Biogen, Cambridge, MA 02142, United States; Translational Cellular Sciences, Biogen, Cambridge, MA 02142, United States; Comparative Medicine, School of Medicine, Yale University, New Haven, CT 06520, United States |
推荐引用方式 GB/T 7714 | Nagy D.,Ennis K.A.,Wei R.,et al. Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration[J],2021,118(6). |
APA | Nagy D..,Ennis K.A..,Wei R..,Su S.C..,Hinckley C.A..,...&Burkly L.C..(2021).Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America,118(6). |
MLA | Nagy D.,et al."Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021). |
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