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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00859

Resveratrol activates autophagy via AKT/mTOR signaling pathway to improve cognitive dysfunction in rats with chronic cerebral hypoperfusion

  • 1Department of Neurology, China-Japan Union Hospital of Jilin University, China
  • 2College of Clinical Medicine, Jilin University, China

Objectives: Effects of resveratrol on autophagy in frontal cortex and hippocampus of CCH model rats were observed, and neuroprotective effects of resveratrol on CCH rats and the mechanism of action of AKT/mTOR signaling pathway were researched. Method: The CCH model was made by permanently ligating the bilateral common carotid arteries. Neurological deficit scores and Morris water maze test were used to test the behavioral changes and the cognitive function of rats; HE and Tunel staining were used to detect pathological and neuronal apoptosis in frontal cortex and hippocampus. ELISA was used to detect oxidative stress factor and brain injury markers. Immunofluorescence and Western blot were used to detect the expression of apoptosis, autophagy and AKT/mTOR signaling pathway-related proteins in frontal cortex and hippocampus. Results: After resveratrol treatment, the neurological function scores of CCH rats were reduced, cognitive dysfunction caused by long-term hypoxia and hypoperfusion was improved, and the pathological damage in frontal cortex and hippocampus was reduced; The expression of oxidative stress and brain injury markers decreased the apoptotic rate of neurons in the frontal cortex and hippocampus. The resveratrol can activate autophagy and inhibit the expression of AKT/mTOR signaling pathway-related proteins. PI3K inhibitor reversed the protective effect of resveratrol. Conclusions: The resveratrol can improve the cognitive function damage of CCH model rats, and reduce the damage of oxidative stress on neurons in frontal cortex and hippocampus by activating autophagy and inhibit neuronal apoptosis. This effect may be regulated by the AKT/mTOR signaling pathway.

Keywords: resveratrol, Akt, mTOR, cognitive dysfunction, chronic cerebral hypoperfusion

Received: 26 Mar 2019; Accepted: 30 Jul 2019.

Edited by:

Mohammad B. Khan, Medical College of Georgia, Augusta University, United States

Reviewed by:

Murali Vijayan, Texas Tech University Health Sciences Center, United States
Md Suhail Alam, University of Notre Dame, United States
Mohammad Farhan, Hamad bin Khalifa University, Qatar  

Copyright: © 2019 Wang, He, Pan, Wang, Ma, Shi and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Zhongxin Xu, Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China, xuzhongxin9999@163.com