Resveratrol alleviates neurological disorders and motor dysfunction in 3-NP induced- Huntington's Disease in rats: Role of activating AMPK/SIRT1/ULK1 autophagy pathway.

Huntington's disease (HD) is a genetic neurodegenerative disease characterized by striatum damage, which results in a number of uncontrollable muscle movements alongside intellectual and cognitive impairment. The progression of HD is accompanied by neuroinflammation, oxidative stress, and neuronal apoptosis. Resveratrol (RESV) is a naturally occurring compound known for its potent antioxidant and anti-inflammatory effects. RESV showed promising neuroprotective effects against Alzheimer's and Parkinson's disease. The current research aims to study the neuroprotective effects of RESV against 3-nitropropionic acid (3-NP)-induced HD. Forty adult male rats were divided equally into four groups as follows: Group 1- normal control group. Group 2- RESV (25 mg/kg/day, p.o) - treated rats. Group 3- rats treated with 3-NP (10 mg/kg/day, i.p). Group 4- rats treated with 3-NP (10 mg/kg/day, i.p) + RESV (25 mg/kg/day, p.o). The results showed that RESV alleviated the behavioral deficits observed in 3-NP treated rats. In addition, the histopathological images showed obvious improvement in RESV-treated rats. RESV activated the AMP-activated protein kinase (AMPK)-related autophagy pathway that resulted in neuroprotection and cell survival. Moreover, RESV showed anti-inflammatory and antioxidant effects by decreasing levels of inflammatory biomarkers including tumor necrosis factor (TNF)-α, nuclear factor kappa (NF-κ)-B, and interleukin (IL)-1β, alongside increasing neuronal antioxidant capacity by stimulating reduced glutathione (GSH), superoxide dismutase (SOD), and preventing lipid peroxidation. In conclusion, our study showed that RESV has a potent neuroprotective effect as evidenced by its ability to significantly alleviate biochemical and behavioral hallmarks of HD.