Overexpression of miR-132-3p contributes to neuronal protection in in vitro and in vivo models of Alzheimer's disease

摘要

One of the neuropathological hallmarks of Alzheimer's disease (AD) is accumulation and deposition of amyloidbeta (A81-42) plaques in the hippocampus. Recently, microRNAs (miRNAs), have been demonstrated to play an essential role in AD. We have previously demonstrated that miR-132-3p exerts neuroprotection via regulating histone deacetylase 3 (HDAC3) in a mouse model of AD. In the present study, we further unveiled neuroprotective roles of miR-132-3p in transgenic amyloid precursor protein/presenilin 1 (APP/PS1) mice compared with those in age-matched wild-type C57BL/6 mice. Lentiviral-mediated inhibition or overexpression of miR132-3p in the hippocampus of APP/PS1 mice was used to explore the contributions of hippocampal miR-1323p in spatial memory, amyloid burden, apoptosis, and the number of hippocampal cells in a mouse model of AD. Overexpression of hippocampal miR-132-3p ameliorated spatial memory deficits in the Morris water maze, reduced both A81-42 accumulation and apoptosis, and promoted the numbers of hippocampal cells in the brains of APP/PS1 mice. Furthermore, trichostatin A (TSA) promoted the expression of miR-132-3p in A81-42-burdened neurons while increasing the expression levels of synaptic proteins. Taken together, our results suggest that miR132-3p may represent a promising therapeutic target for the treatment of AD.

关键词