The Brain at Low Temperature: Tau Hyperphosphorylation Dynamics in Hibernation Torpor

Abstract

Mammalian torpor is associated with neuronal tau protein hyperphosphorylation. This process is fully reversed upon rewarming to euthermy. Not much is known about the hyperphosphorylation dynamics during cooling and rewarming to and from torpor. In this study we show that there is a negative relation between brain temperature and the amount of tau hyperphosphorylation in the cortex of Syrian hamsters. This relation was found to be nonlinear: the fastest changes in the hyperphosphorylation state of the tau protein occurred around brain temperatures of 27°C. The amount of hyperphosphorylation did not substantially increase further with the time spent in torpor. In mice, reversible hyperphosphorylation could also be detected during torpor-like hypothermia at 21°C, but was not present during torpor-like hypothermia at an ambient temperature of 30°C. These results suggest that tau hyperphosphorylation is not only passively connected with brain temperature, but is actively regulated. The results argue against a need for periodic euthermy to reverse hyperphosphorylation of tau in the brain. Alternatively we hypothesise that the phosphorylation of the tau protein may play an active role in the regulation of the neuronal metabolism, facilitating the entrance and or maintenance of the torpid state.