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

• Published in: Behavioural brain research Vol. 366; pp. 118 - 125
• Main Authors: Hu, Xue-Ling, Wang, Xiao-Xue, Zhu, Yan-Meng, Xuan, Li-Na, Peng, Li-Wei, Liu, Yun-Qi, Yang, Hua, Yang, Chao, Jiao, Lei, Hang, Peng-Zhou, Sun, Li-Hua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 02.07.2019
• Subjects: Animals; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cerebral Cortex - blood supply; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cerebrovascular Circulation - physiology; Chronic cerebral hypoperfusion; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Dementia - metabolism; Dementia - pathology; Disease Models, Animal; HEK293 Cells; Hippocampus - blood supply; Hippocampus - metabolism; Hippocampus - pathology; Humans; Male; MicroRNAs - genetics; MicroRNAs - metabolism; miR-132; Nav1.1; NAV1.1 Voltage-Gated Sodium Channel - genetics; NAV1.1 Voltage-Gated Sodium Channel - metabolism; Nav1.2; NAV1.2 Voltage-Gated Sodium Channel - genetics; NAV1.2 Voltage-Gated Sodium Channel - metabolism; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurons - metabolism; Neurons - pathology; Rats; Rats, Sprague-Dawley; Temporal Lobe - pathology; AChE; HEK293T; MWM; AD; AMO; qRT-PCR; PTEN; CCH; CNS; PP2A; 2VO; VD; BACE1; Nav1.2; LAMP-2; miR-132; Nav1.1; TRIM2; GA; Chronic cerebral hypoperfusion; NOS1; FOXO3a; ODNs
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2019.03.026

•miR-132 was decreased in hippocampus and cortex of rats after chronic cerebral hypoperfusion (CCH).•miR-132 improved dementia susceptibility induced by 2VO.•miR-132 prevents CCH-induced learning and memory impairments by down-regulating the expression of Nav1.1 and Nav1.2.•Voltage-gated sodium channel alpha subunit 1(SCN1A) and voltage-gated sodium channel alpha subunit 2 (SCN2A) are the potential target genes of miR-132. 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.