REM-Sleep Deprivation Induces Mitochondrial Biogenesis in the Rat Hippocampus

Abstract

Background/aim: Sleep loss is proposed as a trigger for manic episodes in bipolar disorder in humans. It has been shown that sleep and wakefulness can affect changes in mitochondrial gene expression, oxidative phosphorylation (OXPHOS) activity, and morphology in the brain. In this study, we investigated alterations in mitochondrial bioenergetic function in the brain of rats after 72-h rapid eye movement sleep deprivation (REM-SD).

Materials and methods: Alterations in the mitochondrial DNA (mtDNA) copy number were detected in the prefrontal cortex and hippocampus through amplification of mitochondrially encoded NADH dehydrogenase 1 (mt-Nd1) gene using quantitative real-time polymerase chain reaction. The expression levels of mitochondrial biogenesis-related proteins such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), cytochrome c oxidase subunit 4I1 (COX4I1) and sirtuin 3 (SIRT3) were assessed using western blot analysis and immunohistochemistry.

Results: We found that REM-SD significantly increased the mtDNA copy number in the hippocampus but not in the prefrontal cortex. In addition, REM-SD increased the protein expression of COX4I1 in the hippocampus. Furthermore, we observed manic-like behaviors in rats exposed to 72-h REM-SD. REM-SD increased locomotion in the open-field test and the time spent in open arms in the elevated plus-maze test.

Conclusion: REM-SD may induce mitochondrial dysfunction in the brain, which may be involved in the induction of mania.

Keywords: Mitochondria; hippocampus; manic-like behavior; rapid eye movement sleep deprivation.