Treadmill Exercise During Cerebral Hypoperfusion Has Only Limited Effects on Cognitive Function in Middle-Aged Subcortical Ischemic Vascular Dementia Mice.

Ryo Ohtomo,Gaku Ohtomo,Gen Hamanaka,Ken Arai,Eng H Lo,Kelly K Chung,Hajime Takase,Hidehiro Ishikawa,Hiroshi Katsuki,Christiane D Wrann,Josephine Lok,Atsushi Iwata,Keita Kinoshita

doi:10.3389/fnagi.2021.756537

Abstract

Clinical and basic research suggests that exercise is a safe behavioral intervention and is effective for improving cognitive function in cerebrovascular diseases, including subcortical ischemic vascular dementia (SIVD). However, most of the basic research uses young animals to assess the effects of exercise, although SIVD is an age-related disease. In this study, therefore, we used middle-aged mice to examine how treadmill exercise changes the cognitive function of SIVD mice. As a mouse model of SIVD, prolonged cerebral hypoperfusion was induced in 8-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into two groups: a group that received 6-week treadmill exercise and a sedentary group for observation. After subjecting the mice to multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to only be effective in ameliorating cognitive decline in the Y-maze test. We previously demonstrated that the same regimen of treadmill exercise was effective in young hypoperfused-SIVD mice for all three cognitive tests. Therefore, our study may indicate that treadmill exercise during cerebral hypoperfusion has only limited effects on cognitive function in aging populations.

Highlights

Physical activity helps to promote and maintain brain health, including memory retention and cognitive performance
Our current study demonstrated that in middle-aged mice with prolonged cerebral hypoperfusion, treadmill exercise ameliorates the decline of working memory in the Y-maze test
Treadmill exercise was limited in its supportive effects on cognitive function in the Morris water maze test and novel object recognition test (NORT)

Summary

Introduction

Physical activity helps to promote and maintain brain health, including memory retention and cognitive performance. Research has shown that increased physical activity both prevents and ameliorates multiple brain diseases, including subcortical ischemic vascular dementia (SIVD). There is an emerging body of evidence suggesting that patients with mild VCID perform better at cognitive functioning tests after aerobic exercise (Liu-Ambrose et al, 2016). There is a lack of basic data in experimental models that supports the efficacy of exercise for preventing SIVD/VCID progression. We reported that treadmill exercise improved cognitive function and increased the number of oligodendrocyte precursor cells (OPCs) in the white matter of hypoperfused-SIVD mice (Ohtomo et al, 2020). An important question remains; aging is a major risk factor for SIVD, and the majority of SIVD patients are elderly, no reports to date have examined the efficacy of exercise in aged SIVD mice. In this study, we asked whether treadmill exercise alleviates cognitive decline by cerebral hypoperfusion in 8months old mice

Methods

Results

Conclusion