Delayed Activation of Sirt1 Induced Autophagy Signaling Promotes Astrogliosis, Infarct in Experimental Stroke

Curcumin, a polyphenol, is an active constituent derived from Curcuma longa.The protective nature of curcumin against cerebral ischemia-reperfusion (CIR) is well documented.This study aims evaluate the changes in Sirtuin-1 (Sirt1)induced autophagy signaling.We also investigated the neuroprotective effect of curcumin on Sirt1-mediated autophagy and neuronal survival on day7 post-stroke in a rat model of middle cerebral artery occlusion (MCAO).MCAO was performed for 60 min in male Sprague Dawley rats.Immunoblotting and immunohistochemistry were used to detect alteration in Sirt1 and autophagy-related proteins Beclin-1, autophagy-related genes-3, 5, and 7 (Atg), microtubule-associated protein-1A light chain3 (Lc3-I/II), mammalian target of rapamycin (mTOR), p-mTOR, and cleaved caspase-3.CIR, on day1 post-stroke, resulted in significant alteration of Lc3-II/I and p-mTOR.Further, on day7 post-stroke, Sirt1-induced autophagy decreased, while mTOR phosphorylation and cleaved caspase-3 immunoreactivity increased.Curcumin treatment promoted astrogliosis and infarct.Sirt1-mediated autophagy signaling is involved in the promotion of astrogliosis and infarct.EX-527 blocked the increase in Sirt1/ autophagy signaling evoked by curcumin and reduced astrogliosis and infarct.These findings show that curcumin may promote infarct and reactive astrogliosis via activation of Sirt1/autophagy signaling.