GLP-1 plays a protective role in hippocampal neuronal cells by activating cAMP-CREB-BDNFsignaling pathway against CORT+HG-induced toxicity

Abstract Major depressive disorder (MDD) combined with diabetes mellitus (DM) seriously reduce the quality of life of patients, currently there is still no effective treatment. Our study explores the feasibility of GLP-1 in the treatment of major depressive disorder combined with diabetes mellitus. We aimed to assess the protective effects of GLP-1 on mouse hippocampal neuronal cell line HT22 cultured with corticosterone (CORT) and high glucose (HG). HT22 cells were cultured with CORT + HG to construct cell model of MDD combined with DM. After treatment with GLP-1, cell viability detected by CCK-8 assay, cell apoptosis/necrocytosis detected by flow cytometry/confocal laser scanning microscopy, BDNF and neurotransmitter levels in culture supernatants measured through enzyme-linked immunosorbent assay, LDH and glucose levels in culture supernatants measured via colorimetric assay, and proteins of cAMP-CREB-BDNF signal pathway measured by colorimetric assay Western blot. To construct cell model of MDD combined with DM, the ideal intervention combination are CORT 200µM and HG 50mM for 48 hours. After treatment of 50nM GLP-1 for 48 hours, the apoptosis rate and necrocytosis rate of model + 50nM GLP-1 group decreased significantly compared with the model group. The concentration of BDNF, neurotransmitter (5-HT, DA, NE), PKA, p-CREB and p-Trkb in culture supernatants of model + 50nM GLP-1 group increased significantly compared with the model group. The concentration of grouse and LDH in culture supernatants of model + 50nM GLP-1 group decreased significantly compared with the model group. GLP-1 against CORT + HG-induced toxicity by activating cAMP-CREB-BDNF signaling pathway in hippocampal neuronal cell.