1H-NMR-based metabolomics reveals that prior exercise modulates metabolic changes in the cerebral cortex and
B R D da Silva1, P I G Nunes1, R S de Matos1
1Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Abstract:
Sleep deprivation induces profound metabolic disturbances in the brain, while regular physical exercise is recognized for promoting neuroprotection and energy balance. This study investigated the effects of chronic treadmill exercise on the cortical and hippocampal metabolic profiles of sleep-deprived Swiss mice using the entire 1H-NMR spectrum. Male mice (n=48) were assigned to four groups: Control, Exercise (EX), Sleep Deprivation (SD), and Exercise before Sleep Deprivation (EX+SD). The EX group underwent 8 weeks of aerobic training, and SD was induced by 72-h total sleep deprivation. Brain metabolomic analysis revealed that the cortex and hippocampus shared a qualitatively similar metabolic composition, with taurine, creatine, and lactic acid as the most abundant metabolites. Exercise increased cortical levels of lactic acid, creatine, taurine, and other metabolites involved in glycolysis, the TCA cycle, and osmoregulation, while SD disrupted energy-related metabolites and increased glial markers such as myo-inositol. The EX+SD group exhibited a cortical metabolic profile similar to controls, indicating that prior exercise preserved neuroenergetic balance in this region. In contrast, hippocampal metabolism remained partially affected by SD, despite exercise preconditioning. These findings suggest that exercise confers region-specific metabolic resilience, especially in the cortex, by modulating pathways related to pyruvate metabolism, glutamate turnover, and astrocytic-neuronal coupling. Regular physical activity may thus act as a non-pharmacological strategy to mitigate SD-induced neurochemical imbalances.
