Correcting abnormalities in miR ‐124/PTPN1 signaling rescues tau pathology in Alzheimer’s disease

AbstractMicroRNAs have been implicated in diverse physiological and pathological processes. We previously reported that aberrant microRNA ‐124 (miR‐124)/nonreceptor‐type protein phosphatase 1 (PTPN1) signaling plays an important role in the synaptic disorders associated with Alzheimer's disease (AD). In the current study, we further investigated the potential role of miR‐124/PTPN1 in the tau pathology of AD. We first treated t he mice with intrahippocampal stereotactic injections. Then, we used quantitative real‐time reverse transcription PCR (qRT‐PCR) to detect the expression of microRNAs. Western blotting was used to measure the level of PTPN1, the level of tau protein, the phosphorylation of tau at AD‐related sit es, and alterations in the activity of glycogen synthase kinase 3β (GSK‐3β) and protein phosphatase 2 (PP2A). Immunohistochemistry was also used to detect changes in tau phosphorylation levels at AD‐related sites and somadendritic aggregation. Soluble and insoluble tau protein were separated b y 70% formic acid (FA) extraction to examine tau solubility. Finally, behavioral experiments (including the Morris water maze, fear conditioning and elevated plus maze) were performed to examine learning and memory ability and emotion‐related behavior. We found that artificially replicating the ab normalities in miR‐124/PTPN1 signaling induced AD‐like tau pathology in the hippocampus of wild‐type mice, including hyperphosphorylation at multiple si...

Source: Journal of Neurochemistry - January 16, 2020 Category: Neuroscience Authors: Tong ‐Yao Hou, Yang Zhou, Ling‐Shuang Zhu, Xiong Wang, Pei Pang, Ding‐Qi Wang, Zhen‐Yu Liuyang, Hengye Man, Youming Lu, Ling‐Qiang Zhu, Dan Liu Tags: ORIGINAL ARTICLE Source Type: research