Effect of Epigallocatechin Gallate and Catechin on Overexpression of GSK-3β and IR Genes Induced by Streptozotocin in Rat Brain

Background: Type 2 diabetes mellitus (T2DM) is one of the significant risk factors for Alzheimer disease (AD). Defects in insulin signaling pathway induce AD hallmarks mainly through activation of glycogen synthase kinase-3β (GSK-3β) pathway.  Objectives: In this study, we investigated the expression of GSK-3β and insulin receptor (IR) genes in the hippocampi of an animal model of sporadic AD and assessed the preventive effect of Catechin (CAT) and epigallocatechin gallate (EGCG) on their expression. Materials & Methods: Adult male Wistar rats were treated by intracerebroventricular streptozotocin (STZ) injection (3 mg/kg) at day 1 and 3 after cannulation. CAT was administered at a dose of 40 mg/kg for 10 days per gavage, and EGCG was administered at a dose of 3 mg/kg for 14 days into drinking water. Then the animals were decapitated, and their hippocampi were removed. Real-time Polymerase Chain Reaction (PCR) was used to evaluate the alteration in gene expression. Results: There was overexpression in GSK-3β gene in STZ-treated rats (P≤0.05), which was brought back to normalcy by EGCG (P≤0.01). The IR gene also increased after STZ treatment, but CAT reduced IR expression (P≤0.05). However, the suppressive effect of EGCG on IR expression was stronger (P≤0.01).  Conclusion: The neuroprotective activity of EGCG might be due to its influence on IR and GSK-3β expression