Molecular mechanisms of seasonal brain shrinkage and regrowth in Sorex araneus

Human brains typically grow through development, then remain the same size in adulthood, and often shrink through age-related degeneration that induces cognitive decline and impaired functionality. In most cases, however, the neural and organismal changes that accompany shrinkage, especially early in the process, remain unknown. Paralleling neurodegenerative phenotypes, the Eurasian common shrew Sorex araneus, shrinks its brain in autumn through winter, but then reverses this process by rapidly regrowing the brain come spring. To identify the molecular underpinnings and parallels to human neurodegeneration of this unique brain size change, we analyzed multi-organ, season-specific transcriptomics and metabolomic data. Simultaneous with brain shrinkage, we discovered system-wide metabolic shifts from lipid to glucose metabolism, as well as neuroprotection of brain metabolic homeostasis through reduced cholesterol efflux. These mechanisms rely on a finely tuned brain-liver crosstalk tha...