Title:miR-132 Down-regulates Methyl CpG Binding Protein 2 (MeCP2) During Cognitive Dysfunction Following Chronic Cerebral Hypoperfusion
VOLUME: 14 ISSUE: 4
Author(s):Zhao-Hui Yao *, Xiao-li Yao , Yong Zhang , Shao-feng Zhang and Jichang Hu
Affiliation:Department of Geriatrics, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, Department of Neurology, Central Hospital of Zhengzhou, #195 Tongbo Road, Zhengzhou, Department of Neurology, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, Department of Neurology, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, Department of Pathology, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan
Keywords:Methyl CpG binding protein 2, miR-132, cognition dysfunction, chronic cerebral hypoperfusion, vascular dementia,
vascular risk factor.
Abstract: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.
