当前位置： SCI文献检索 > BEHAVIOURAL BRAIN RESEARCH期刊下所有文献 > MicroRNA-132 regulates total protein of Nav1.1 and Nav1.2 in the hippocampus and cortex of rat with chronic cerebral hypoperfusion.

MicroRNA-132 regulates total protein of Nav1.1 and Nav1.2 in the hippocampus and cortex of rat with chronic cerebral hypoperfusion.

Abstract：

:Nav1.1 and Nav1.2 are the voltage-gated sodium channel alpha subunit1 and 2, encoded by the genes of SCN1A and SCN2A. Previous studies have shown that chronic cerebral hypoperfusion (CCH) could induce neuropathological and cognitive impairment and increased total Nav1.1 and Nav1.2protein levels, yet the detailed mechanisms are not fully understood. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the regulation of dementia. miR-132 is known to play a key role in neurodegenerative disease. Here, we determined that miR-132 regulates Nav1.1 and Nav1.2 under CCH state. In this study, the expression of miR-132 was decreased in both the hippocampus and cortex of ratsfollowing CCH generated by bilateral common carotid artery occlusion (2VO). Lentiviral-mediated overexpression of miR-132 ameliorated dementia vulnerability induced by 2VO. At the molecular level, miR-132 repressed the increased protein expression of Nav1.1 and Nav1.2 in both the hippocampus and cortex induced by 2VO. MiR-132 suppressed, while AMO-miR-132 enhanced, the level of Nav1.1 and Nav1.2 in primary cultured neonatal rat neurons (NRNs) detected by both western blot analysis and immunofluorescence analysis. Results obtained by dual luciferase assay showed that overexpression of miR-132 inhibited the expression of Nav1.1 and Nav1.2 in human embryonic kidney 293 (HEK293T) cells. Additionally, binding-site mutation failed to influence Nav1.1 and Nav1.2, indicating that Nav1.1 and Nav1.2 are potential targets for miR-132. Taken together, our findings demonstrated that miR-132 protects against CCH-induced learning and memory impairments by down-regulating the expression of Nav1.1 and Nav1.2, and SCN1A and SCN2A are the target genes of miR-132.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Hu XL,Wang XX,Zhu YM,Xuan LN,Peng LW,Liu YQ,Yang H,Yang C,Jiao L,Hang PZ,Sun LH

doi

10.1016/j.bbr.2019.03.026

subject

Has Abstract

pub_date

2019-07-02 00:00:00

pages

118-125

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(18)31628-0

journal_volume

366

pub_type

杂志文章

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