Abstract: Objective: To investigate the neuroprotective effect of resveratrol (Res) on tunicamycin (TM)-induced endoplasmic reticulum stress (ERS) and its mechanism. Methods: Fetal hippocampal neurons from female mice at 18 days of pregnancy were used for primary culture. The experiment was divided into a control group (without drug treatment), a TM group (2.5 μg/mL), a Res group (5 μmol/L) and a Res + TM group (5 μmol/L Res + 2.5 μg/mL TM). Cell Counting Kit-8 (CCK8) was used to detect the survival rate of hippocampal neurons and the optimal concentration and action time of TM and Res were determined. Flow cytometry was used to detect the cell apoptosis and cycle of primary neurons, and Western blot was used to analyze the expression of proteins related to endoplasmic reticulum stress, autophagy, apoptosis and cell cycle. Results: Preconditioning with Res (5 μmol/L) for 10 h could reduce the inhibitory effect of TM on the survival rate of primary neurons and reactivate the cell cycle of neurons, promoting its transition from G1/G0 to S phase. Compared with the TM group, preconditioning with Res for 10 h significantly decreased the relative expression levels of glucose-regulated protein 78 (GRP78) (P < 0.01), caspase 3 (P < 0.05), but significantly increased the protein expression levels of autophagy-related protein Beclin-1 (P < 0.05) , microtubule-associated protein 1 light chain 3B (LC3B) (P < 0.05), phosphorylated glycogen synthase kinase 3β (p-GSK3β) (P < 0.001) and apoptosis-related protein B-cell lymphoma 2 (Bcl2) (P < 0.01), as well as inhibited cell apoptosis induced by TM. Conclusion: Res can attenuate TM-induced ERS in primary neurons and protect primary neurons. The mechanism is related to the regulation of Res on cell survival rate, cell cycle distribution and the expression of autophagy- and apoptosis-related proteins.

Key words: resveratrol; primary neuron; Alzheimer’s disease; endoplasmic reticulum stress; apoptosis and autophagy