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Untargeted-metabolomics of mice cortex subjected to sleep deprivation – the modifying effects of exercise


Sleep deprivation/restriction (SD) occur in association with sleep disorders such as insomnia and sleep apnea. Cognitive impairment and dementia are also associated with these sleep disturbances. Exercise has been found to have a positive influence on sleep and on cognitive impairment and dementia. It has recently been shown that several metabolites are altered in the brain in association with sleep fragmentation


The aim of this study was to evaluate the effects of chronic aerobic exercise on metabolomics of the cortex of mice subjected to sleep deprivation.


Three-month-old swiss mice were divided into four groups: control, SD, exercise (EX) and previous exercise followed by SD (EX+SD). Exercised animals were submitted to motorized treadmill (9m / s) for 8 weeks. Sleep deprived mice were submitted to the modified multiple platform model (72h). The metabolite profiles of mice cortex, in all groups, were analyzed using liquid chromatography/mass spectrometry.


A deep chemometrics analysis revealed distinctive metabolic profiles between the SD, EX+SD, EX and Control groups. Aerobic exercises induced the production of lactate, n-acetylaspartic acid, creatine, taurine while a decrement of the content of ethanol, alanine, gamma-aminobutyric acid, myo-inositol, choline, and acetate was observed. Sleep deprivation induces acetate production while decreasing the content of ethanol, lactate, alanine, gamma-aminobutyric acid (GABA), n-acetyl aspartic acid, creatine, choline, taurine and myo-inositol in the cortex. Importantly, the cortex from EX+SD mice and control samples presented a similar composition.


This untargeted metabolomics study shows that previous exercise reestablished scores of SD mice cortex to similar values as in control. These findings provide further mechanistic explanation for the beneficial effects of exercise in conditions of sleep deprivation/restriction that commonly occurs in many sleep disorders


Metabolomics. Cortex. Sleep deprivation. Exercise. Mice. Brain


Área Básica


Bruna Rafaele Diógenes Silva, Paulo Iury Gomes Nunes, Lorena Mara Alexandre Silva, Elenilson Godoy Alves-Filho, Edy Souza Brito, Pedro Felipe Carvalhedo Bruin, Veralice Meireles Sales Bruin