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

  • Ryo Ohtomo
  • Keita Kinoshita
  • Gaku Ohtomo
  • Hajime Takase
  • Gen Hamanaka
  • Kazuo Washida
  • Mohammad Rashedul Islam
  • Christiane D. Wrann
  • Hiroshi Katsuki
  • Atsushi Iwata
  • Josephine Lok
  • Eng H. Lo
  • Ken AraiEmail author
Short Communication


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.


Treadmill exercise Subcortical ischemic vascular dementia White matter Oligodendrocyte precursor cell Subventricular zone 



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

Author 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.

Funding Information

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

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

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.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ryo Ohtomo
    • 1
    • 2
  • Keita Kinoshita
    • 3
  • Gaku Ohtomo
    • 2
  • Hajime Takase
    • 1
  • Gen Hamanaka
    • 1
  • Kazuo Washida
    • 1
  • Mohammad Rashedul Islam
    • 4
  • Christiane D. Wrann
    • 4
  • Hiroshi Katsuki
    • 3
  • Atsushi Iwata
    • 2
  • Josephine Lok
    • 1
  • Eng H. Lo
    • 1
  • Ken Arai
    • 1
    Email author
  1. 1.Neuroprotection Research Laboratory, Departments of Radiology and NeurologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA
  2. 2.Department of NeurologyThe University of Tokyo Graduate School of MedicineTokyoJapan
  3. 3.Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical SciencesKumamoto UniversityKumamotoJapan
  4. 4.Cardiovascular Research Center, Department of MedicineMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA

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