Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling

• DOI: 10.1007/s11011-021-00751-2
• Publication Date: 2021-05-18T08:03:17Z
• Authors: Aliasghar Zarezad...; Junyoung Hong; Jonghae Lee; Hamid Rajabi; Reza Gharakhanlu; Naser Naghdi; Mohammad Azimi; Yoonjung Park
• Keywords: Male; Vascular Endothelial Growth Factor A; 0301 basic medicine; Amyloid beta-Peptides; Hippocampus; Rats; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Alzheimer Disease; Animals; Cognitive Dysfunction; Rats, Wistar; Maze Learning; Angiostatins

Abstract Vascular endothelial growth factor (VEGF) regulates angio/neurogenesis and also tightly links to the pathogenesis of Alzheimer’s disease (AD). Although exercise has a beneficial effect on neurovascular function and cognitive function, the direct effect of exercise on VEGF-related signaling and cognitive deficit in AD are incompletely understood. Therefore, the purpose of this study was to investigate the protective effect of exercise on angiostatin/VEGF cascade and cognitive function in AD model rats. Wistar male rats were randomly divided into five groups: control (CON), injection of DMSO (Sham-CON), CON-exercise (sham-EX), intrahippocampal injection of Aβ (AD), and AD-exercise (AD-EX). Rats in EX groups underwent treadmill exercise for 4 weeks, then the cognitive function was measured by the Morris Water Maze (MWM) test. mRNA levels of HIF-1, VEGF, VEGFR2, and angiostatin were determined by RT-PCR. We found that cognitive function was impaired in AD rats, but exercise training improved it. Moreover, exercise training increased the reduced mRNA expression level of VEGF signaling, including HIF1α, VEGF, and VEGFR2 in the hippocampus from AD rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from AD rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in AD, possibly through enhancing VEGF signaling and reducing angiostatin.