气候变化领域集成服务门户(CCPortal): Altered Cl− homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability

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DOI	10.1073/pnas.2016034118
	Altered Cl− homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability
	Maset A.; Galla L.; Francia S.; Cozzolino O.; Capasso P.; Goisis R.C.; Losi G.; Lombardo A.; Ratto G.M.; Lodovichi C.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Impairments of inhibitory circuits are at the basis of most, if not all, cognitive deficits. The impact of OPHN1, a gene associate with intellectual disability (ID), on inhibitory neurons remains elusive. We addressed this issue by analyzing the postnatal migration of inhibitory interneurons derived from the subventricular zone in a validated mouse model of ID (OPHN1−/y mice). We found that the speed and directionality of migrating neuroblasts were deeply perturbed in OPHN1−/y mice. The significant reduction in speed was due to altered chloride (Cl−) homeostasis, while the overactivation of the OPHN1 downstream signaling pathway, RhoA kinase (ROCK), caused abnormalities in the directionality of the neuroblast progression in mutants. Blocking the cation-Cl− cotransporter KCC2 almost completely rescued the migration speed while proper directionality was restored upon ROCK inhibition. Our data unveil a strong impact of OPHN1 on GABAergic inhibitory interneurons and identify putative targets for successful therapeutic approaches. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	2P imaging; Cl homeostasis; Intellectual disability; Interneuron migration; OPHN1
语种	英语
scopus关键词	cation; doublecortin; fasudil; green fluorescent protein; potassium chloride cotransporter 2; RhoA guanine nucleotide binding protein; animal experiment; animal model; animal tissue; Article; cell maturation; cell migration; cell transport; cellular distribution; chloride homeostasis; controlled study; enzyme activity; enzyme inhibition; forebrain; GABAergic system; gene; homeostasis; intellectual impairment; interneuron; loss of function mutation; mouse; mouse model; mutant; nerve cell plasticity; neuroblast; nonhuman; OPHN1 gene; priority journal; protein expression; signal transduction; subventricular zone
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181080
作者单位	Veneto Institute of Molecular Medicine, Padua, 35129, Italy; Padova Neuroscience Center, Padova, 35129, Italy; Department of Biomedical Sciences, University of Padua, Padua, 35131, Italy; Neuroscience Institute, National Research Council, Padua, 35127, Italy; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genoa, 16132, Italy; Istituto Nanoscienze, Consiglio Nazionale delle Ricerche, Pisa, 56127, Italy; National Enterprise for nanoScience and nanoTechnology, Scuola Normale Superiore, Pisa, 56127, Italy; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; Vita-Salute San Raffaele University, Milan, 20132, Italy
推荐引用方式 GB/T 7714	Maset A.,Galla L.,Francia S.,et al. Altered Cl− homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability[J],2021,118(2).
APA	Maset A..,Galla L..,Francia S..,Cozzolino O..,Capasso P..,...&Lodovichi C..(2021).Altered Cl− homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Maset A.,et al."Altered Cl− homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).