Brain inflammatory cytokines and microglia morphology changes throughout hibernation phases in Syrian hamster

Abstract

Hibernators tolerate low metabolism, reduced cerebral blood flow and hypothermia during torpor without noticeable neuronal or synaptic dysfunction upon arousal. Previous studies found extensive changes in brain during torpor, including synaptic rearrangements, documented both morphologically and molecularly. As such adaptations may represent organ damage, we anticipated an inflammatory response in brain during specific hibernation phases. In this study, signs of inflammation in the brain were investigated in the Syrian hamster hippocampus (Mesocricetus Auratus) both during hibernation (torpor and arousal phases) and in summer and winter euthermic animals.mRNA expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β was quantified by RT-qPCR. Morphological changes of microglia were studied by immunohistochemistry staining for IBA-1. Activation of microglia based on retraction and thickening of the dendritic branches and an increase in cell body size was quantified by calculation of cell body size to total cell size ratio.Expression of pro-inflammatory cytokines was upregulated early in arousal (90 min), and normalized after 8 h of arousal. Substantial loss of microglia ramification was found throughout torpor and early arousal together with a 2-fold increase in the cell body size to total cell size ratio. Notably, microglia changes were fully reversed in late arousal (8 h) to euthermic levels.These results demonstrate an upregulation of inflammatory cytokines and signs of microglia activation during hibernation, which completely resolves by late arousal. Activation of this response may serve to prevent or offset brain damage resulting from the substantial physiological changes accompanying torpor and their rapid change during early arousal.