Exercise Alleviates Behavioral Disorders but Shapes Brain Metabolism of APP/PS1 Mice in a Region- and Exercise-Specific Manner

Exercise plays a beneficial role in the management of Alzheimer's disease (AD), but its effects on brain metabolism are still far from being understood. Here, we examined behavioral changes of APP/PS1 mice after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) and analyzed metabolomics profiles in the hippocampus, cortex, and hypothalamus by using nuclear magnetic resonance spectroscopy to explore potential metabolic mechanisms. The results demonstrate that both HIIT and MICT alleviated anxiety/depressive-like behaviors as well as learning and memory impairments of AD mice. Metabolomics analysis reveals that energy metabolism, neurotransmitter metabolism, and membrane metabolism were significantly altered in all three brain regions after both types of exercises. Amino acid metabolism was detected to be affected in the cortex and hypothalamus after HIIT and in the hippocampus and hypothalamus after MICT. However, only HIIT significantly altered astrocyte-neuron metabolism in the hippocampus and hypothalamus of AD mice. Therefore, our study suggests that exercise can shape brain metabolism of AD mice in a region-and exercise-specific manner, indicating that the precise modification of brain metabolism by a specific type of exercise might be a novel perspective for the prevention and treatment of AD.

Automated summary

Exercise, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), can improve behavioral and cognitive impairments in Alzheimer's disease (AD) mice. Metabolomics analysis reveals significant changes in energy metabolism, neurotransmitter metabolism, and membrane metabolism in multiple brain regions after both types of exercises. HIIT also alters astrocyte-neuron metabolism in the hippocampus and hypothalamus of AD mice. These findings suggest that exercise can modulate brain metabolism in a region- and exercise-specific manner, potentially providing a novel approach for the prevention and treatment of AD.