Comparing prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 diabetes mellitus
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Department of Medical Physiology, Kasr Alainy Faculty of Medicine, Cairo University, Egypt
Department of Biochemistry, Faculty of Medicine, Cairo University, Egypt
Department of Anatomy and Embryology, Faculty of Medicine, Assiut University, Egypt
Department of Histology and Cytology, Faculty of Medicine, Alazhar University, Egypt
Department of Pathology and Laboratory Medicine, VAMC North East Ohio Healthcare System, Louis Stokes, Cleveland, Ohio, USA
Submission date: 2019-07-29
Final revision date: 2020-03-10
Acceptance date: 2020-03-26
Online publication date: 2020-09-16
Type 2 diabetes mellitus (DM) and Alzheimer’s disease (AD) are two major medical conditions that constitute a significant financial burden on most healthcare systems. Due to AD sharing “insulin resistance” mechanistic features with DM, some scientists have proposed “type 3 DM” terminology for it. This study aims to compare the prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 DM.

Material and methods:
Two groups of rats were included in the study: the control group (n = 15) and the streptozotocin-induced type 2 diabetic group (n = 45). The diabetic group was subdivided into three equal subgroups: a sedentary non-treated diabetic group, an exercised group, and a metformin-treated group. We estimated step-down avoidance task latency, serum glucose, insulin, free fatty acids (FFA), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG), brain A-42 and glucose, histological changes by toluidine blue, and immunohistochemistry for brain Aβ-42 and tau-positive cells.

Serum glucose, FFA, TG, cholesterol, LDL, brain Aβ-42, brain glucose, the number of hippocampal dark and degenerated cells, and brain Aβ-42 and tau-positive cells, were all significantly lower. In contrast, serum insulin and HDL, the number of hippocampal granular cells, and latency of the step-down avoidance task were significantly higher in exercised and metformin-treated groups compared to the diabetic group. There were significantly higher values of serum insulin and brain/plasma glucose ratio and number of brain tau-positive cells in the metformin-treated group than in the exercised group.

We can conclude that exercise can be as effective as metformin regarding prophylaxis against the deleterious effects of type 3 DM on cognitive brain functions.