Cognitive impairment in Alzheimer's disease (AD) is usually accompanied by synaptic loss in both the hippocampus and neocortex. In the early stage of AD, amyloid β-induced synapse changes is the main reason, while in the later stage, the accumulation of Tau protein promotes synapse degeneration as the key factor leading to dementia. MicroRNA (miRNA) is closely related to the expression changes of many AD-related genes. One of the most abundant brain-enriched miRNAs is miR-132, which has been shown to regulate both neuron morphogenesis and plasticity. It has been reported that miR-132 is significantly reduced in the brains of Alzheimer's patients. Genetic deletion of miR-132 in mice promotes Aβ deposition, leading to impaired memory and enhanced Tau pathology, but how the miRNA-mediated gene expression dysregulation contributes to AD pathology remains unclear. Here we found the possible downstream target of miR-132 by in silico analysis, namely C1q. C1q is the primary protein of classical complement cascade, which is highly expressed in the synaptic regions of the central nervous system in Alzheimer's patients. However, it is not clear whether miR-132 plays a role in AD through regulating C1q. To address this question, the APP/PS1 transgenic mice were transfected with miR-132 and given C1 inhibitors. Behavior tests were conducted to assess memory and cognitive abilities seven days after administration. In addition, we analyzed the expression of PSD95, Synapsin-1 and phosphorylated (p)-Synapsin. We found that the expression levels of the synaptic proteins treated with miR-132 or C1INH were significantly increased compared with the AD group. Further RT-qPCR result suggested that miR-132 might regulate C1q expression in AD.

中文翻译：

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miR-132通过C1q调节APP / PS1转基因小鼠中突触蛋白的表达。

阿尔茨海默氏病（AD）的认知障碍通常伴有海马和新皮层的突触丧失。在AD的早期，淀粉样β诱导的突触变化是主要原因，而在后期，Tau蛋白的积累促进突触变性，这是导致痴呆的关键因素。MicroRNA（miRNA）与许多AD相关基因的表达变化密切相关。大脑中最丰富的miRNA之一是miR-132，它已显示出可以调节神经元形态和可塑性。据报道，阿尔茨海默氏病患者的大脑中miR-132明显降低。小鼠miR-132的基因缺失可促进Aβ沉积，从而导致记忆受损和Tau病理增强，但尚不清楚miRNA介导的基因表达失调如何导致AD病理。在这里，我们通过计算机分析发现了miR-132的可能下游靶标，即C1q。C1q是经典补体级联反应的主要蛋白，在老年痴呆症患者的中枢神经系统突触区域高表达。但是，尚不清楚miR-132是否通过调节C1q在AD中发挥作用。为了解决这个问题，用miR-132转染APP / PS1转基因小鼠并给予C1抑制剂。给药后7天进行行为测试以评估记忆力和认知能力。此外，我们分析了PSD95，Synapsin-1和磷酸化（p）-Synapsin的表达。我们发现，与AD组相比，用miR-132或C1INH处理的突触蛋白的表达水平显着提高。进一步的RT-qPCR结果表明miR-132可能调节AD中的C1q表达。