Effects of lithium on brain oxidative stress in C57BL/6 mice subjected to paradoxical sleep deprivation and different rest periods.

Abstract

Previous studies indicate that humans and rodents subjected to paradoxical sleep deprivation (PSD) exhibit changes in oxidative stress parameters. However, the protective effects of sleep in reversing oxidative damage caused by PSD, as well as the combination of sleep and lithium (Li) have not yet been investigated. This study evaluated oxidative stress parameters in the brains of C57BL/6 mice at different time points of rest after 36 h of PSD. Mice were pretreated with saline or Li for seven days to observe the effects of Li. The PSD protocol lasted 36 h, followed by rest periods of 0, 24, 48, or 72 h. Biochemical analyses were conducted in the frontal cortex, striatum, and hippocampus, assessing reactive oxygen species production (DCFH), oxidative lipid damage [thiobarbituric acid reactive substances (TBARS), 4-hydroxy-2-nonenal (4-HNE), 8-isoprostane (8-ISO)], and antioxidant capacity [superoxide dismutase (SOD) activity, glutathione (GSH) levels]. PSD increased 4-HNE in all regions and 8-ISO in the frontal cortex and striatum, while Li prevented PSD-induced oxidative damage. SOD activity and GSH levels remained unchanged. Oxidative damage from PSD was reversed at 24, 48, and 72 h of rest. However, 48 h after PSD, Li-pretreated mice showed elevated oxidative damage markers, which normalized by 72 h. This study is the first to assess long-term oxidative damage from PSD and its interaction with Li, highlighting the need for further research on sleep deprivation, Li, and rest duration in the context of bipolar mania.