Resveratrol delays 6-hydroxydopamine-induced apoptosis by activating the PI3K/Akt signaling pathway

Abstract

This study aimed to determine whether resveratrol (Res) delays the progression of 6-hydroxydopamine (6-OHDA)-induced apoptosis via activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Sprague-Dawley (SD) rats were unilaterally injected with 6-OHDA (8 μg/4 μL) into the substantia nigra of the midbrain. Res (15 and 30 mg/kg) was given orally to the rats for a total of 36 days to examine its protective effects. We first tested whether Res can delay the progression of 6-OHDA-induced damage by measuring weight and performance on behavioral tests (rotarod, open field test and grid test) and further explored whether this effect is related to the activation of the PI3K/Akt signaling pathway using immunohistochemistry (IHC) and Western blotting (WB). Our results showed that the damage induced by 6-OHDA gradually worsened, while Res 30 mg/kg treatment significantly improved motor function and increased body weight. Compared with those in the model group, the number of dopaminergic neurons cells and the expression of PI3K-110α, p-Akt Ser473, and pro-caspase-3 in the Res 30 mg/kg group were significantly increased, and the Bax/Bcl-2 ratio and the level of activated caspase-3 was decreased. The results indicate that Res ameliorates 6-OHDA-induced apoptosis and motor dysfunction via activating the PI3K/Akt signaling pathway, delaying the progression of Parkinson's disease (PD) symptoms in this model.

Keywords: 6-Hydroxydopamine; Parkinson's disease; Phosphoinositide 3-kinase; Protein kinase B; Resveratrol.