The cool brain: How hibernators maintain neuronal integrity

Deep hibernation is an energy-saving strategy, characterized by long torpor periods (4-20 days) of extreme metabolic suppression and low body temperature, interspaced by short arousal periods (12-16h) of euthermia and high energy expenditure. Despite extensive research, the function to which the costs of these arousals are traded-off is unknown. During torpor, hibernators build up hyperphosphorylated tau, a phenomenon associated with neurodegenerative diseases like Alzheimer’s, but in hibernators this is completely reversed during euthermic arousal. Interestingly, animals sleep most of the time during arousals, suggesting an adaptive function. However, the role of arousal sleep and the reversal of tau hyperphosphorylation are still a mystery in hibernation research. The key objectives of this hibernation proposal is to understand why torpor is regularly interrupted by arousals and whether sleep influences the reversal of tau hyperphosphorylation, and how hyperphosphorylated tau influences hibernation and arousal sleep. We expect that hyperphosphorylated tau levels could trigger arousals to occur in time to prevent injury. Because there was no prior wakefulness, arousal sleep is an unexplained behaviour. We suggest arousal sleep plays an essential role in the reversal of tau hyperphosphorylation. An additional objective is to determine whether DNA damage during torpor induces cellular senescence in neurons or glial cells, and if this influences tau hyperphosphorylation and arousal. Recent evidence suggests senescence to drive tau hyperphosphorylation and we hypothesize therefore that it could drive this process during hibernation. The final objective is to examine if the torpor body temperature influences torpor-associated tissue remodelling. We will use the garden dormouse as model, capable of deep hibernation at various temperatures. State of the art techniques in neuroscience allow for modulation of tau hyperphosphorylation in non-model animals like the garden dormouse. Ultimately, the results from this benefits the understanding of the hibernation trade-off, and may lead to novel biomedical applications.