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

Qi Ma; Li Wang; Xiang-Xin Liu; Zhi-Guo An; Xiao Luo; Li-Li Zhang; Ping Yan; Lu Jin; Ren Cai; Qi-Zhong Yi

doi:10.1016/j.heliyon.2023.e18491

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

Heliyon. 2023 Jul 22;9(8):e18491. doi: 10.1016/j.heliyon.2023.e18491. eCollection 2023 Aug.

Authors

Qi Ma¹, Li Wang¹, Xiang-Xin Liu^{2

3}, Zhi-Guo An⁴, Xiao Luo⁴, Li-Li Zhang⁴, Ping Yan⁴, Lu Jin⁴, Ren Cai⁵, Qi-Zhong Yi^{4

6}

Affiliations

¹ State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
² Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, China.
³ Department of Psychological Medicine, First People's Hospital of Kashi Region, Kashi, 844000, China.
⁴ Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
⁵ Specimen Bank of Xinjiang Key Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
⁶ Xinjiang Clinical Research Center for Mental Health, Urumqi, 830054, China.

Abstract

Major depressive disorder (MDD) with diabetes mellitus (DM) significantly reduces the quality of the patient's life, and currently, there is no effective treatment. This study explored the feasibility of Glucagon-like peptide-1 (GLP-1) in treating MDD combined with DM. The protective effects of GLP-1 on mouse hippocampal neuronal cell line HT22 cultured with corticosterone (CORT) and high glucose (HG) were assessed. HT22 cells were cultured with CORT + HG to construct a cell model of MDD combined with DM. Cell viability and cell apoptosis/necrocytosis were detected by CCK-8 assay and flow cytometry/confocal laser scanning microscopy, respectively, after treatment with GLP-1. In addition, BDNF and neurotransmitter levels, lactic dehydrogenase (LDH) and glucose levels, and proteins of cAMP-CREB-BDNF signal pathway in the culture supernatants were measured through an enzyme-linked immunosorbent assay and colorimetric assays and Western blot, respectively. The ideal intervention combination to construct a cell model of MDD combined with DM was CORT 200 μM and HG 50 mM for 48 h. After treatment of 50 nM GLP-1 for 48 h, the model+50 nM GLP-1 group's apoptosis and necrocytosis rates and LDH and glucose concentrations in the culture supernatants decreased significantly compared with the model group. However, the BDNF, 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), PKA, p-CREB, and p-Trkb concentrations in the culture supernatants increased significantly. GLP-1 functioned against CORT + HG-induced toxicity by activating the cAMP-CREB-BDNF signaling pathway in hippocampal neuronal cells.

Keywords: Diabetes mellitus; GLP-1; HT22; Major depressive disorder; cAMP-CREB-BDNF pathway.