Maheu, M. G. | Search bioRxiv

bioRxiv2026

Can you run from your worries? The effects of exercise on anxiety-like behaviour and immune signaling in female and male mice

Exercise is a positive health behaviour associated with improved mood. However, the mechanisms underlying the benefits of exercise on affective health are unclear, particularly with respect to type of exercise and sex. Chronic exercise decreases neuroinflammation, which is linked to improvements in mood and anxiety. However, exercise is also a physiological stressor that can transiently upregulate systemic inflammation, and its effects on neuroinflammation are not well understood. This study examined how acute and chronic exercise affect circulating and brain cytokine levels and anxiety-related behaviour in young healthy male and female mice. In Experiment 1, mice were placed on a treadmill for a two-hour bout of moderate exercise. Two hours after exercise, animals were either tested in the open field or euthanized for measurement of cytokines (IL-1{beta}, TNF, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IFN-{gamma}, KC/GRO). In Experiment 2, mice underwent an 8-week moderate treadmill exercise paradigm followed by open field testing and tissue collection. Acute exercise decreased time spent in the centre of the open field in males only, suggesting increased anxiety-like behaviour in males. Acute exercise increased IL-6 and decreased TNF in serum, and increased amygdala principal component 1 (loading IL-12p70, IL-10, IFN-{gamma}, and TNF) in both sexes. Chronic exercise increased open field centre entries, increased IL-6 in the prefrontal cortex, decreased TNF in the dorsal hippocampus, and had minimal effects on circulating cytokines in both sexes. These results demonstrate that the effects of exercise on anxiety-related behaviour and cytokine levels depend on recurrence, tissue, and brain region. NEW & NOTEWORTHYOur work highlights the contrast between anxiogenic and anxiolytic effects of acute versus chronic exercise, respectively, in healthy mice. Acute and chronic exercise differentially affected circulating and brain cytokines, providing insight into physiological adaptations to exercise. Both sexes demonstrated similar cytokine responses to exercise. These similarities are novel with respect to exercise research and noteworthy given sex differences in anxiety with respect to acute exercise.

neuroscience↗

bioRxiv2023

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

Exercise is accepted as a positive health behaviour; however, the mechanisms of exercise on neuroprotection and cognitive health are not completely understood. The purpose of this study 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. Adult mice were assigned to a sedentary or treadmill exercise group for eight weeks. During the final week, 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 and probe trial. 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 proportions of microglia type (ameboid, stout/thick, and thick/thin) were regulated by exercise in the ventral dentate gyrus. We conclude that exercise decreases PNNs in the dentate gyrus in both sexes and this may be related to better spatial learning and memory.

neuroscience↗