Abstract
Sleep deprivation is a potent stress factor that disrupts regulatory pathways in the brain resulting in cognitive dysfunction and increased risk of neurodegenerative disease with increasing age. Prevention of the adverse effects of sleep deprivation could be beneficial in older individuals by restoring healthy brain function. We report here on the ability of SS31, a mitochondrial specific peptide, to attenuate the negative neurological effects of short-term sleep deprivation in aging mice. C57BL/6 female mice, 20 months old, were subcutaneously injected with SS31 (3 mg/kg) or saline daily for four days. Sleep deprivation was 4 h daily for the last two days of SS31 treatment. Mice were immediately tested for learning ability followed by collection of brain and other tissues. In sleep deprived mice treated with SS31, learning impairment was prevented, brain mitochondrial ATP levels and synaptic plasticity regulatory proteins were restored, and reactive oxygen species (ROS) and inflammatory cytokines levels were decreased in the hippocampus. This observation suggests possible therapeutic benefits of SS31 for alleviating adverse neurological effects of short-term sleep loss.
Highlights
Studies have shown that sleep plays a vital role in brain plasticity and memory [1,2] and ensures efficacy of electrical firing within the neuronal synapse [3,4]
Aging C57BL/6 mice, treated with the mitochondrial-targeted peptide SS31 daily for 4 days and sleep deprived on the third and fourth days of treatment, do not show the learning impairment seen in age-matched sleep deprived control mice but have nearly normal learning ability similar to non-sleep deprived mice
Sleep deprived mice treated with SS31 showed suppression of mitochondrial reactive oxygen species (ROS) and enhanced ATP production in the brain and liver
Summary
Studies have shown that sleep plays a vital role in brain plasticity and memory [1,2] and ensures efficacy of electrical firing within the neuronal synapse [3,4]. SS31 (D-Arg-dimethylTyr-Lys-Phe-NH2), a synthetic mitochondrial-specific peptide, has been shown to improve synaptic and cognitive impairments in mice and rats exposed to lipopolysaccharide and isoflurane [13,14,15]. In another study, aged mice treated with SS31 displayed significantly improved neurovascular coupling responses and cognitive functions, including spatial working memory and motor skill learning [16]. The effect of SS31 on learning impairment associated with short-term sleep deprivation in aging mice has not yet been investigated. The effect3o26f SS31 on learning impairment associated with short-term sleep deprivation in aging mice has not yet breepeonritntvheastigSaSt3e1d.pWreevesnhotewd ilneathrnisinregpiomrtptahiartmSeSn3t1ipnreovldenmtedicelearfnteirngshimorpt-atierrmmenstleienpolddempriicveaatifotenr, sahnodrpt-rtoervmidesldeaetpa dsuegpgrievsatitniognt,haenpdroptercotvivideeeffdeacttas saureggmeesdtiinagtedthbeypproretseecrtivviengefmfeictotschaornedmrieadl iantedgrbity panredsesyrvnianpgtimc iftuoncchtoionnd.rial integrity and synaptic function
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