Brain-Derived Neurotrophic Factor as A Target for Metformin in Treatment of Type 2 Diabetes Mellitus-Associated Cognitive Changes
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- Category: Vol. 85, December 2017
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Brain-Derived Neurotrophic Factor as A Target for Metformin in Treatment of Type 2 Diabetes Mellitus-Associated Cognitive Changes, OMAIMA M. ABD EL-WAHED, OLA M. TORK, MAHA M. GAMAL EL-DIN, LAILA RASHED and MAHA ZICKRI
Abstract
Aim: The current study investigated the effect of anti-diabetic drug Metformin on Type 2 Diabetes Mellitus (T2DM)associated cognitive changes and potential role of Brain-derived Neurotrophic Factor (BDNF).
Methods: A total of 36 adult male wistar albino rats were divided into 4 groups; control, Metformin control, diabetic and Metformin treated groups. At the end of the study, Y-Maze and open field tests were done to assess cognitive functions. Serum fasting glucose, insulin and lipid profile were measured. Homeostasis model assessment insulin resistance was calculated. Gene expression of BDNF, area of degenerated neurons and area % of synaptophysin immunocxpression were examined in the brain tissue.
Results: Diabetic rats exhibited a severe deficit in memory and locomotion associated with hyperglycemia, insulin resistance, dyslipidemia, neurodegeneration, reduced BDNF and synaptophysin expression in the brain tissue. In contrast, treatment with Metformin (100mg/kg body weight once each morning for 4 weeks) reversed these changes, and hence improved cognitive performance and synaptic function.
Conclusion: The present study demonstrates that treatment of T2DМ with Metformin upregulates BDNF in the brain, maintains neuronal survival and synaptic integrity, and consequently, enhances cognitive performance in diabetic rats.