Investigating The Adaptive Role Of Brain Mitochondria In A Mammalian Hibernator

During the hibernation season, thirteen-lined ground squirrels (Ictidomys tridecemlineatus) regularly cycle between bouts of torpor and interbout arousal (IBA). This presents a unique seasonal change in energy requirements in the brain. Most of the brain is electrically quiescent during torpor, but regains activity upon arousal to IBA, resulting in extreme oscillations in energy demand during the hibernation season. We predicted that brain mitochondria undergo a seasonal change in function to accommodate the variable energy demands of hibernation. To address this hypothesis, we examined mitochondrial bioenergetics of brain in thirteen-lined ground squirrels across four time points: Summer (SU), Fall (FA), Hibernation (HIB) and Spring (SP). Respiration rates of isolated brain mitochondria were measured using an oxygen electrode with three substrates: Glutamate/Malate, Succinate, and Glycerol-3-Phosphate. Membrane potential (mV) and proton leak were measured simultaneously using a TPP+ electrode. Glutamate/Malate-fueled respiration was significantly higher in HIB than in both SU and FA (p<0.05). Succinate-fueled respiration was significantly lower (p<0.05) in SP and SU than in HIB. We found no significant difference in mV between SP, SU and FA. These data imply that brain mitochondrial bioenergetics are not static across the year, and suggest that the brain requires more fuel and resources to function efficiently during hibernation. This study provides essential underpinnings to understanding the overall energy requirements of a hibernator's brain and provides clues to into the neuroprotective strategies employed by a mammalian hibernator.