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

• Published in: Metabolic brain disease 2021-12, Vol.36 (8), p.2263-2271
• Main Authors: Zarezadehmehrizi, Aliasghar, Hong, Junyoung, Lee, Jonghae, Rajabi, Hamid, Gharakhanlu, Reza, Naghdi, Naser, Azimi, Mohammad, Park, Yoonjung
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid beta-Peptides - pharmacology; Angiostatin; Angiostatins - metabolism; Angiostatins - pharmacology; Animal models; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cognitive ability; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - therapy; Disease Models, Animal; Fitness training programs; Gene expression; Growth factors; Hippocampus; Hippocampus - metabolism; Hypoxia; Hypoxia-inducible factor 1a; Injection; Male; Maze Learning; Metabolic Diseases; Neurodegenerative diseases; Neurogenesis; Neurology; Neurosciences; Oncology; Original Article; Pathogenesis; Physical training; Polymerase chain reaction; Rats; Rats, Wistar; Rodents; Signaling; Spatial discrimination learning; Spatial memory; Training; Treadmills; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptor 2; Vascular endothelial growth factor receptors
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-021-00751-2

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 is 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 (Aβ), and Aβ-exercise (Aβ-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 hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and angiostatin were determined in hippocampus by RT-PCR. We found that spatial learning and memory were impaired in Aβ-injected 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 Aβ-injected rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from Aβ-injected rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in Aβ-injected rats, possibly through enhancing VEGF signaling and reducing angiostatin.