Impact of Metformin on Cognition Impairment in Type 2 Diabetic Male Albino Rats

Abstract

Background: There is controversy around metformin benefits, an insulin-sensitizing drug that is frequently administered, for enhancing cognitive performance in type 2 diabetic mellitus (T2DM) patients which increases cognitive impairment risk. Objectives: This study aims to assess the ameliorative effects of metformin on T2DM-induced cognitive impairment. Materials and methods: Rats were randomly assigned to three groups: group I (Control), group II (Diabetic), and group III (Diabetic-Metformin). Streptozotocin (STZ) (30 mg/kg, i.p.) administered as single dose to groups II and III following ten-week high-fat diet. Group III received metformin for ten weeks. Hippocampal memory examined using T Maze and novel object cognition tests were performed before animal scarification. Hippocampal samples were extracted at experiment end for biochemical (TNFα, IL-1β levels), histological and immunohistochemical (Bcl2/Bax ratio) studies. Results: Group III showed a significant increase in spontaneous alternation in T-maze test (76.67% ± 15.02) compared to group II (6.67% ± 10.32) (p < 0.001). Significant increase in discrimination ratio in novel object recognition test was observed in group III after treatment (0.111 ± 0.02) compared to before treatment (-0.0466 ± 0.015) (P < 0.05). There was increase in Bcl-2/Bax ratio expression (2.794 ± 0.59) after treatment compared to before treatment (0.294 ± 0.08) (P < 0.001). Metformin decreased levels of TNFα and IL-1β in diabetic rats from (753.2 ± 86.3), (455.7 ± 43.6) respectively, to (372.1 ± 48.1), (220.1 ± 16.3) (P < 0.001). Conclusion: Our results suggest that metformin may be promising drug for improving T2DM-induced cognitive dysfunction by reducing harmful pathophysiological effects.

Keywords

• t2dm apoptosis inflammation metformin
• cognition impairment bcl2/bax ratio