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

Authors：Zeng, Chong; Meng, Xingjun; Mai, Dongmei; Xu, Kai; Qu, Shaogang^*

Source：Behavioural Brain Research, 2022, 417: 113584.

DOI：10.1016/j.bbr.2021.113584

• Alzheimer's disease
• miR-132-3p
• Trichostatin A
• HDAC3
• Neuronal protection

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.

• Institution
  1; 南方医科大学