Effect of Exenatide on Apoptosis, Autophagy, and Necroptosis in the Hippocampus of STZ-Induced Diabetic Female Rats: An Immunohistochemical Study

Document Type : Original Article


1 Human Anatomy and Embryology, Faculty of Medicine, Port Said University, Egypt

2 Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt


Introduction: Diabetes mellitus has serious consequences on all body systems, and the hippocampus is a vulnerable site for this affection. The study aims to examine the effect of exenatide treatment on the diabetic rats` hippocampal oxidative stress, apoptosis, autophagy, and necroptosis. Materials and methods: Twenty-four adult female albino rats were divided into four groups: control, diabetic (received a single intraperitoneal injection of streptozotocin (STZ) at a dose of 45 mg/kg), treated (received a single intraperitoneal injection of STZ and daily intraperitoneal injection of exenatide at a dose of 1 µg/kg for 10 weeks), and exenatide (received daily intraperitoneal injection of exenatide for 10 weeks). After 10 weeks, blood samples were collected for measuring blood glucose levels, and hippocampi were dissected out. Tissue homogenates of the hippocampus from one hemisphere were used for oxidative stress markers. The other hemisphere was processed for histopathological and immunohistochemical stain using caspase 3, microtubule-associated protein light chain 3 (LC3b), p62, and receptor-interacting kinase (RIP3) antibodies. Results: Oxidative stress was evident in the diabetic hippocampus, with insignificant improvement with exenatide treatment. Apoptosis was detected in CA1, CA3, and dentate gyrus (DG), and significant improvement was noticed with exenatide treatment mainly in DG. Autophagy was impaired in all hippocampal regions, and exenatide significantly improved its activity. Necroptosis was detected mainly in diabetic CA1, although not significant when compared with other groups. Conclusion: Histopathological improvement resulting from exenatide treatment is mainly due to reducing hippocampal neuronal apoptosis and restoring autophagy, while the effect on necroptosis was non-significant.