Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Chronic cerebral hypoperfusion (CCH) is a significant cause of vascular dementia and other neurological disorders.
• Limited therapeutic options exist for CCH, highlighting the need for novel treatments.

Purpose of the Study:

• To investigate the therapeutic potential of resveratrol in a rat model of CCH.
• To elucidate the underlying mechanisms of resveratrol's action, focusing on autophagy and the AKT/mTOR signaling pathway.

Main Methods:

• A rat model of CCH was established using bilateral common carotid artery occlusion.
• Neurological deficit scores, cognitive function (Morris water maze), and histological changes were assessed.
• Molecular mechanisms were explored using TUNEL staining, ELISAs, and Western blot to analyze autophagy and AKT/mTOR signaling.

Main Results:

• Resveratrol significantly reduced neurological deficits and pathological damage in the frontal cortex and hippocampus of CCH rats.
• Resveratrol activated autophagy and inhibited the expression of AKT/mTOR signaling pathway proteins.
• Inhibition of phosphoinositide-3 kinase reversed the protective effects of resveratrol.

Conclusions:

• Resveratrol demonstrates therapeutic efficacy in improving cognitive function and mitigating neuronal damage in CCH.
• The neuroprotective effects of resveratrol are mediated by the activation of autophagy and modulation of the AKT/mTOR signaling pathway.
• Resveratrol represents a potential therapeutic agent for CCH and related neurological conditions.