气候变化领域集成服务门户(CCPortal): miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release

CCPortal

DOI	10.1073/pnas.2021770118
	miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release
	Lu S.-Y.; Fu C.-L.; Liang L.; Yang B.; Shen W.; Wang Q.-W.; Chen Y.; Chen Y.-F.; Liu Y.-N.; Zhu L.; Zhao J.; Shi W.; Mi S.; Yao J.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that miR-218-2 but not miR-218-1 could bidirectionally regulate the contextual and spatial memory in the mice. Furthermore, miR-218-2 deficiency induced deficits in the morphology and presynaptic neurotransmitter release in the hippocampus to impair the long term potentiation. Combining the RNA sequencing analysis and luciferase reporter assay, we identified complement component 3 (C3) as a main target gene of miR-218 in the hippocampus to regulate the presynaptic functions. Finally, we showed that restoring the C3 activity in the miR-218-2 KO mice could rescue the synaptic and learning deficits. Therefore, miR-218-2 played an important role in the cognitive functions of mice through C3, which can be a mechanism for the defective cognition of miR-218 related neuronal disorders. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	C3; Hippocampus; LTP; miR-218; Synapse
语种	英语
scopus关键词	complement component C3; microRNA; microRNA 218 1; microRNA 218 2; unclassified drug; adult; animal cell; animal experiment; animal model; Article; brain function; cognition; controlled study; female; gene control; gene identification; gene overexpression; gene targeting; genetic analysis; hippocampal neuronal culture; hippocampus; in vivo study; learning disorder; long term potentiation; luciferase assay; memory disorder; mouse; nerve cell plasticity; neurotransmitter release; newborn; nonhuman; pathogenesis; phenotype; presynaptic nerve; priority journal; protein function; RNA sequencing; spatial memory; synapse vesicle; synaptic transmission
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/179967
作者单位	State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG, McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, 100084, China; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Beihang University, Beijing, 100191, China
推荐引用方式 GB/T 7714	Lu S.-Y.,Fu C.-L.,Liang L.,et al. miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release[J],2021,118(14).
APA	Lu S.-Y..,Fu C.-L..,Liang L..,Yang B..,Shen W..,...&Yao J..(2021).miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Lu S.-Y.,et al."miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).