LAUSR

ABSTRACT 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&bgr; and neuronal apoptosis induced by CCH. Interestingly, GSK‐3&bgr;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&bgr;. Therefore, nimodipine may be a candidate for the treatment of tauopathy present in CCH.