One of the neuropathological hallmarks of Alzheimer’s disease (AD) is accumulation and deposition of amyloid-beta (Aβ) 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 miR-132-3p in the hippocampus of APP/PS1 mice was used to explore the contributions of hippocampal miR-132-3p 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 Aβ 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 Aβ-burdened neurons while increasing the expression levels of synaptic proteins. Taken together, our results suggest that miR-132-3p may represent a promising therapeutic target for the treatment of AD.

中文翻译：

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miR-132-3p 的过表达有助于阿尔茨海默病体外和体内模型中的神经元保护


阿尔茨海默病 (AD) 的神经病理学标志之一是海马中淀粉样蛋白 - β (Aβ) 斑块的积累和沉积。最近，microRNA (miRNA) 已被证明在 AD 中发挥重要作用。我们之前已经证明，miR-132-3p 通过调节组蛋白脱乙酰酶 3 (HDAC3) 在 AD 小鼠模型中发挥神经保护作用。在本研究中，我们进一步揭示了与年龄匹配的野生型C57BL/6小鼠相比，miR-132-3p在转基因淀粉样前体蛋白/早老素1（APP/PS1）小鼠中的神经保护作用。采用慢病毒介导的 APP/PS1 小鼠海马 miR-132-3p 抑制或过表达来探讨海马 miR-132-3p 在空间记忆、淀粉样蛋白负荷、细胞凋亡和海马细胞数量中的贡献。 AD小鼠模型。海马 miR-132-3p 的过度表达改善了 Morris 水迷宫中的空间记忆缺陷，减少了 Aβ 积累和细胞凋亡，并增加了 APP/PS1 小鼠大脑中海马细胞的数量。此外，曲古抑菌素 A (TSA) 促进 Aβ 神经元中 miR-132-3p 的表达，同时增加突触蛋白的表达水平。综上所述，我们的结果表明 miR-132-3p 可能是治疗 AD 的一个有前途的治疗靶点。