PMID- 29090669 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20190508 IS - 1875-5739 (Electronic) IS - 1567-2026 (Linking) VI - 14 IP - 4 DP - 2017 TI - miR-132 Down-regulates Methyl CpG Binding Protein 2 (MeCP2) During Cognitive Dysfunction Following Chronic Cerebral Hypoperfusion. PG - 385-396 LID - 10.2174/1567202614666171101115308 [doi] AB - BACKGROUND: Chronic Cerebral Hypoperfusion (CCH) is an important vascular risk factor for vascular-related dementia cognitive impairment and there are no effective measures for the prevention and treatment of cognitive deficit by CCH and the underlying mechanisms are still poorly understood. Methyl cytidine-phosphate-guanosine (CpG) binding protein 2 (MeCP2), regulated by microRNA 132 (miR-132), is as a transcriptional repressor in high concentrations in the brain, which regulates the expression of synaptic proteins and neuroplasticity, and may be involved in the cognitive deficit after CCH. But no relevant studies have been reported. The aim of this study is to investigate the status of MeCP2 expression after CCH and explore whether MeCP2 changes is associated with cognitive deficits after CCH. METHODS: We investigated MeCP2 expression after CCH using Western blotting, quantitative Real- Time Polymerase Chain Reaction (qRT-PCR) analysis and immunofluorescence technique in a rat model of permanent bilateral common carotid artery occlusion (2VO) to mimic CCH. We determined the effect of MeCP2 expression on cognitive deficits and neuroplasticity after CCH through lenti-virus stereotaxic injection, the Morris water maze and electrophysiology. RESULTS: CCH contributed to the down-regulation of MeCP2 and mecp2 expressions in the hippocampus and cortex. miR-132 up-regulated by 2VO was distinctly negatively correlated with MeCP2 down-regulation by miR-132 inhibitors. MeCP2 over-expression improved learning and memory impairment, as well as neuroplasticity after 2VO. Brain-Derived Neurotrophic Factor (BDNF) and the activities of its downstream pathways moleculars, tropomyosin receptor kinase B (TrkB) and the cAMP Response Element Binding Protein (CREB) were down-regulated by 2VO and rescued by MeCP2 over-expression. CONCLUSION: Our study found that miR-132 may participate in the down-regulation of MeCP2 after CCH and MeCP2 down-regulation was possibly involved in the cognitive deficit through regulation of BDNF and its downstream pathways after 2VO. Our findings expounded the underlying mechanisms of cognition deficit after CCH, which contributes to understanding the mechanisms of vascular dementia. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Yao, Zhao-Hui AU - Yao ZH AD - Department of Geriatrics, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, China. FAU - Yao, Xiao-Li AU - Yao XL AD - Department of Neurology, Central Hospital of Zhengzhou, #195 Tongbo Road, Zhengzhou, China. FAU - Zhang, Yong AU - Zhang Y AD - Department of Neurology, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, China. FAU - Zhang, Shao-Feng AU - Zhang SF AD - Department of Neurology, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, China. FAU - Hu, Jichang AU - Hu J AD - Department of Pathology, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United Arab Emirates TA - Curr Neurovasc Res JT - Current neurovascular research JID - 101208439 RN - 0 (MIRN132 microRNA, rat) RN - 0 (Mecp2 protein, rat) RN - 0 (Methyl-CpG-Binding Protein 2) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Cerebrovascular Circulation/*physiology MH - Cerebrovascular Disorders/complications/*metabolism MH - Chronic Disease MH - Cognitive Dysfunction/etiology/*metabolism MH - Down-Regulation/*physiology MH - Male MH - Maze Learning/physiology MH - Methyl-CpG-Binding Protein 2/antagonists & inhibitors/*metabolism MH - MicroRNAs/*biosynthesis MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Methyl CpG binding protein 2 OT - chronic cerebral hypoperfusion OT - cognition dysfunction OT - miR-132 OT - vascular dementia OT - vascular risk factor EDAT- 2017/11/02 06:00 MHDA- 2019/05/09 06:00 CRDT- 2017/11/02 06:00 PHST- 2017/07/22 00:00 [received] PHST- 2017/10/08 00:00 [revised] PHST- 2017/10/10 00:00 [accepted] PHST- 2017/11/02 06:00 [pubmed] PHST- 2019/05/09 06:00 [medline] PHST- 2017/11/02 06:00 [entrez] AID - CNR-EPUB-86633 [pii] AID - 10.2174/1567202614666171101115308 [doi] PST - ppublish SO - Curr Neurovasc Res. 2017;14(4):385-396. doi: 10.2174/1567202614666171101115308.