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Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion

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Abstract

Clinical evidence suggests that patients with subcortical ischemic vascular dementia (SIVD) perform better at cognitive tests after exercise. However, the underlying mechanism for this effect is largely unknown. Here, we examined how treadmill exercise changes the cognitive function and white matter cellular pathology in a mouse model of SIVD. Prolonged cerebral hypoperfusion was induced in 2-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into a group that received 6-week treadmill exercise and a sedentary group for observation. In multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to ameliorate cognitive decline in the hypoperfused SIVD mice. In addition, immunohistological analyses confirmed that there was a larger population of oligodendrocyte precursor cells in the subventricular zone of exercised versus sedentary mice. Although further investigations are needed to confirm a causal link between these findings, our study establishes a model and cellular foundation for investigating the mechanisms through which exercise preserves cognitive function in SIVD.

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Acknowledgments

The authors thank Nobuhiro Okagaki and Shuntaro Oribe for technical assistance.

Funding

This study was funded by the National Institutes of Health (R01 NS065089, P01 NS055104, R01 AG055559, R01 NS113556, R01 NS110818) and JSPS KAKENHI (16H05319).

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Authors and Affiliations

  1. Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, MGH East 149-2401, Charlestown, MA, 02129, USA

    Ryo Ohtomo, Hajime Takase, Gen Hamanaka, Kazuo Washida, Josephine Lok, Eng H. Lo & Ken Arai

  2. Department of Neurology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

    Ryo Ohtomo, Gaku Ohtomo & Atsushi Iwata

  3. Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 862-0973, Japan

    Keita Kinoshita & Hiroshi Katsuki

  4. Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA

    Mohammad Rashedul Islam & Christiane D. Wrann

Authors
  1. Ryo Ohtomo
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  2. Keita Kinoshita
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  3. Gaku Ohtomo
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  4. Hajime Takase
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  6. Kazuo Washida
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  9. Hiroshi Katsuki
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  10. Atsushi Iwata
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  11. Josephine Lok
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  12. Eng H. Lo
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  13. Ken Arai
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Contributions

RO, CDW, HK, AI, JL, EHL, and KA designed the study, analyzed and interpreted the data, and wrote the manuscript. RO, KK, GO, HT, GH, KW, and MRI performed the experiments.

Corresponding author

Correspondence to Ken Arai.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Ohtomo, R., Kinoshita, K., Ohtomo, G. et al. Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion. Transl. Stroke Res. 11, 496–502 (2020). https://doi.org/10.1007/s12975-019-00734-7

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  • DOI: https://doi.org/10.1007/s12975-019-00734-7

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