Common transcriptional changes in the brain during hibernation and Alzheimer’s disease

Hibernation demands rapid brain adaptations, involving cycles of reduced metabolic rate during torpor, followed by brief periods of arousal. Previous studies show hibernation induces a drastic increase in Tau hyperphosphorylation, but a mechanistic connection to disease remains unclear. Using single-nucleus RNA sequencing on hippocampi of golden hamsters, we unveil large transcriptional shifts across the hibernation cycle in all cell types, especially glia. Common transcriptional changes in mitochondrial and ribosomal genes are observed in all different cell types. In addition, hibernation triggers an inflammatory-like response in microglia that in part resembles cell states observed in Alzheimer’s disease, but here in the absence of Aβ-accumulation and neurodegeneration. These findings reveal brain transformations that might help preserve vital functions under extreme conditions and they suggest that early cellular changes in AD may be a natural adaptive process.