Glucagon-like peptide-1 protects the murine hippocampus against stressors via Akt and ERK1/2 signaling

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive dysfunction and neuronal cell death in the hippocampus and cerebral cortex. Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptides. GLP-1-associated medicines are widely used as treatments for type 2 diabetes. In addition, they have been shown to ameliorate pathology in AD mouse models. Here, we investigated the effects of GLP-1 on different stressors in murine hippocampal HT22 cells. GLP-1 (7-36) prevented H2O2-, L-glutamate-, tunicamycin-, thapsigargin-, and amyloid beta(1-42)-induced neuronal cell death in a concentration-dependent manner. GLP-1 (7-36) treatment for 1 h significantly increased phosphorylated Ala and extracellular signal-regulated kinase 1 and 2 (ERK1/2) when compared with vehicle-treatment. These results suggest that GLP-1 (7-36) is protective against these stressors via activation of survival signaling molecules, such as Akt and ERK1/2 in HT22 cells. In conclusion, GLP-1 and activators of the GLP-1 receptor might be useful targets for the treatment of AD. (C) 2015 Elsevier Inc. All rights reserved.