Effects of 4-month running exercise on the spatial learning ability and white matter volume and microvessels of middle-aged female and male rats.

Age-related degeneration of microvessels is known to occur in white matter, and exercise training can enhance brain function and promote cerebral blood flow. However, the effects of exercise training on microvessels in aged white matter are unknown. Forty-one middle-aged male and female Sprague-Dawley rats were randomly divided into a sedentary group and an exercised group. The rats in the exercised group were made to run on treadmills for 4 months. The spatial learning capacities of all groups were then assessed with the Morris water maze. White matter and its microvessels were investigated using immunohistological techniques and stereological methods. In the exercised group, females but not males, showed improved performance over time in the Morris water maze. In females but not males, the exercised rats showed significantly increased white matter volume compared with that of sedentary rats. The total length of microvessels in the white matter in the exercised group was significantly increased compared with that in the sedentary group in both males and females, but the total volume and total surface area of microvessels in the white matter did not differ significantly between the sedentary and exercised rats. Regular treadmill exercise had protective effects on spatial learning capacity, white matter volume, and the total length of microvessels in the white matter in middle-aged female rats and on the total length of microvessels in the white matter in middle-aged male rats. The results obtained might increase our understanding of the mechanisms by which exercise delays brain aging.