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

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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 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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

We express our gratitude to the Kharazmi University of Tehran for financial support. The authors would also like to thank the Trabiat Modarres University for the use of experimental equipment.

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Authors and Affiliations

  1. Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA

    Aliasghar Zarezadehmehrizi, Junyoung Hong, Jonghae Lee & Yoonjung Park

  2. Department of Exercise Physiology, Faculty of Physical Education and Sport Science, Kharazmi University, Tehran, Iran

    Aliasghar Zarezadehmehrizi & Hamid Rajabi

  3. Department of Physical Education and Sport Science, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran

    Reza Gharakhanlu & Mohammad Azimi

  4. Department of Physiology and Pharmacology, Pasteur Institute of Iran 13164, Tehran, Iran

    Naser Naghdi

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  1. Aliasghar Zarezadehmehrizi
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  2. Junyoung Hong
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  3. Jonghae Lee
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Contributions

AZ, JH, YP, and HR designed the study, collected and analyzed data. RG and NN involved behavioral study. AZ and MA performed animal experiment. AZ and JH wrote the manuscript. YP, JL, and HR edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yoonjung Park.

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The animal experiments were carried out in accordance with the National Institutes of Health (NIH) Guideline for the Care and Use of Laboratory Animals and were approved by the Ethics Committee on the use of animals at Tarbiat Modares University, Tehran, Iran.

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All the authors declare that they have no conflict of interest.

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Aliasghar Zarezadehmehrizi and Junyoung Hong have contributed equally to this work.

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Zarezadehmehrizi, A., Hong, J., Lee, J. et al. Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling. Metab Brain Dis 36, 2263–2271 (2021). https://doi.org/10.1007/s11011-021-00751-2

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