Abstract: Objective: To investigate the protective effect and underlying mechanism of resveratrol (RSV) on cerebral nerve cells in aging mice induced by D-galactose (D-gal). Methods: An aging mouse model was established by intraperitoneal injection of D-gal. The changes in body mass and brain index (brain/body mass ratio) were calculated. Apoptotic rate, reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) in cerebral cortical neurons were measured by flow cytometry. Mitochondrial caspase-9 and caspase-3 activity were measured, and the difference in the expression of mitochondrial and cytoplasmic cytochrome c (Cyt c) was analyzed by Western blotting. Results: There was no significant difference in body mass among all groups within the experimental period (P > 0.05). Brain index decreased significantly in the aging model group (P < 0.05), the number of times the mice crossed the hidden platform declined and the apoptotic rate of neurons significantly increased (P < 0.01) compared with the normal group, indicating that D-gal significantly damaged nerve cells in mice. Brain index in all three RSV treatment groups especially at a dose of 25.00 mg/kg mb was significantly higher than in the model group (P < 0.01), the number of times the mice crossed the hidden platform increased but with no significance (P > 0.05), and the apoptotic rate of nerve cells declined significantly (P < 0.01), leading to the conclusion that RSV has a protective effect on cerebral neural cells of D-gal-induced aging mice. ROS content in nerve cells of the model group increased significantly (P < 0.01), and MMP significantly decreased compared with the normal group (P < 0.01). Moreover, the expression of mitochondrial Cyt c decreased, the expression of cytoplasmic Cyt c increased, and mitochondrial caspase-9 and caspase-3 activity increased significantly in the model group (P < 0.01), indicating that D-gal could lead to mitochondrial damage. Compared with the model group, ROS level in nerve cells significantly decreased in the RSV groups (P < 0.01); MMP significantly increased (P < 0.01); the expression of mitochondrial Cyt c significantly increased, while the expression of cytoplasmic Cyt c significantly decreased (P < 0.05); and the activity of caspase-9 and caspase-3 significantly decreased (P < 0.01), indicating that resveratrol exerts its protective effect on nerve cells of aging mice through the mitochondrial pathways. Conclusion: Resveratrol can protect cerebral nerve cells of aging mice induced by D-gal through the mitochondrial pathways.

Key words: resveratrol, D-galactose, apoptosis, neuroprotection, mitochondrial pathway