Nimodipine attenuates tau phosphorylation at Ser396 via miR-132/GSK-3β pathway in chronic cerebral hypoperfusion rats

作者：Tan, Zihu; Chen, Yan^*; Xie, Wenting; Liu, Xi; Zhu, Yuanyue; Zhu, Yan

来源：European Journal of Pharmacology, 2018, 819: 1-8.

DOI：10.1016/j.ejphar.2017.10.027

• Chronic cerebral hypoperfusion
• Tau phosphorylation
• GSK-3 beta
• miR-132
• Nimodipine
• Rat

Chronic cerebral hypofusion (CCH) promotes hyperphosphorylation of tau proteins, a key neuropathological trait that reflects neurodegenerative disorders. Nimodipine, an L-type calcium channel antagonist, has been reported to show neuroprotective effects. In this study, we investigated the potential mechanism of nimodipine in tauopathies induced by CCH. MiR-132 is downregulated in tauopathies such as AD and directly targets tau mRNA to regulate its expression. Here, we report that CCH induced miR-132 deficiency and increased tau phosphorylation at Ser396 while tau expression was not influenced. Nimodipine treatment attenuated CCH induced tau phosphorylation by up-regulating expression of miR-132. Furthermore, nimodipine inhibited activation of GSK-3 beta and neuronal apoptosis induced by CCH. Interestingly, GSK-3 beta mRNA level negatively correlated with the expression of miR-132. These findings support a role for nimodipine inhibiting tau phosphorylation at Ser396 via miR-132/GSK-3 beta. Therefore, nimodipine may be a candidate for the treatment of tauopathy present in CCH.

• 出版日期2018-1-15
• 单位南京中医药大学; 湖北省中医院; 湖北中医药大学