Exercise type–brain region interactions determine the effects of exercise on the hippocampus

RYUKI TSUCHIDA^1,2Taisei Yamaguchi¹Ryunosuke Naochi¹Daisuke Funabashi³Takeshi Nishijima^1*

• ¹Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Japan
• ²Japan Society for the Promotion of Science (JSPS) Research Fellowship for Young Scientists., Tokyo, Japan
• ³Hakuo Daigaku, Oyama, Japan

Exercise enhances hippocampal function, which is critical for learning and memory, and dementia prevention. However, the effects of exercise depend not only on the intensity and frequency but also on the type of exercise, and not all exercise reliably activates the hippocampal circuits. Here, we compared treadmill exercise (TE) and rotarod exercise (RE) in mice to determine whether exercise type differentially influences neural activity and hippocampal plasticity across brain regions. In the acute exercise experiments, TE robustly increased neuronal activation in the dorsal hippocampus and entorhinal cortex. In contrast, RE activated other brain regions, including the ventral hippocampus and dorsal raphe nucleus, but failed to increase activity specifically in the dorsal hippocampus–entorhinal pathway. In the chronic phase experiments, both TE and RE produced antidepressant effects, whereas only TE stimulated hippocampal neurogenesis. These results demonstrate that the effects of exercise on the brain are influenced by interactions between the exercise type and brain region. Our findings demonstrate the region-specific and exercise type-dependent characteristics of exercise-induced brain plasticity, underscoring the importance of considering the exercise type when aiming to promote hippocampal health and prevent dementia.