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

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 cogni...

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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
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creator Zarezadehmehrizi, Aliasghar
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description 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.
doi_str_mv 10.1007/s11011-021-00751-2
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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. 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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
title Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling
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