In garden dormouse cerebral cortex, specific transcriptional programs exist for all major phases of hibernation

Abstract

Hibernators cycle between torpor, a state of profound metabolic and thermoregulatory suppression, and brief arousals during which metabolic rate and body temperature rapidly return to euthermic levels. These repeated physiological pressures require robust mechanisms to preserve brain integrity. Because the cerebral cortex is not thought to control hibernation directly yet must remain viable throughout torpor and recover rapidly during arousal, it provides a useful model for studying neural adaptation to hibernation. We therefore performed RNA sequencing of cerebral cortex from garden dormice (Eliomys quercinus) sampled during summer euthermia (SE), early torpor (TE), late torpor (TL), early arousal (AE), and late arousal (AL). Differential expression analysis revealed strongly stage-specific transcriptional remodeling across the hibernation cycle. Entry into torpor (SE-TE) and the transition from early to late arousal (AE-AL) showed minimal change, with 16 and 2 differentially expressed genes (DEGs), respectively. In contrast, extensive regulation was observed during torpor progression (TE-TL; 576 DEGs) and especially during the transition from late torpor to early arousal (TL-AE; 697 DEGs). Intermediate numbers of DEGs were detected in AL-TE (260) and AL-SE (50). Principal component and enrichment analyses indicated that the dominant axes of variation were associated with RNA processing and proteostatic control, metabolic and redox-related adaptation, and changes in intracellular trafficking and protein handling. In addition, comparison of adjacent contrasts revealed a marked opposite-direction transcriptional reversal between TE-TL and TL-AE, consistent with coordinated reactivation of torpor-associated programs during arousal. Together, these findings support a model in which cortex adaptation to hibernation involves transcriptional reprogramming consistent with metabolic suppression during torpor progression, especially in pathways related to carbohydrate and central carbon metabolism, redox homeostasis, and cellular signalling, followed by rapid reversal of these programs during early arousal.