Running to remember: The effects of exercise on perineuronal nets, microglia, and hippocampal angiogenesis in female and male mice

Abstract

Exercise is accepted as a positive health behaviour; however, a less commonly known benefit of exercise is its role in neuroprotection and cognitive health. The purpose of this investigation was to explore the neurobiological benefits of chronic treadmill exercise in female and male mice through its role in microglial content and morphology, cerebral vascularization, and perineuronal net (PNN) expression. We further examined how these neurobiological changes relate to spatial memory outcomes. C57BL/6J mice were assigned to a sedentary (12F/12M) or exercise group (11F/12M). Mice were treadmill-trained for an hour per day, five days per week, at an increasing speed and incline for eight weeks. During the final week of the exercise intervention, all mice were trained on a spatial memory task (Barnes Maze) and brains were collected for immunohistochemistry. Exercised mice made fewer errors than sedentary mice during the first two days of training as well as the probe, which assessed spatial reference memory. Females, regardless of exercise training, made fewer errors during Barnes maze training, and demonstrated a greater frequency of spatial strategy use compared to males. Exercised mice, regardless of sex, had fewer PNNs in the dentate gyrus of the hippocampus compared to sedentary controls. The number of PNNs in the dorsal dentate gyrus was positively correlated with total errors during training. During the probe, greater errors correlated with more PNNs among the exercised group only. Microglia count and cerebral vascularization were not affected by exercise, although exercise mice had significantly fewer thin microglia compared to stout microglia in the ventral dentate gyrus, which was not observed in the sedentary group. We conclude that exercise decreases PNNs in the dentate gyrus in both sexes and this may be related to better spatial learning and memory.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

* Discussion of the manuscript was updated. Figure 3 was revised.