neurodegeneration

Brain plasticity, the brain’s inherent ability to adapt its structure and function, is crucial for responding to environmental challenges but is usually not linked to a significant change in size. A striking exception to this is Dehnel’s phenomenon, where seasonal reversible brain-size reduction occurs in some small mammals to decrease metabolic demands during resource-scarce winter months. Despite these volumetric changes being well documented, the specific microstructural alterations that facilitate this adaptation remain poorly understood. Our study employed diffusion microstructure imaging (DMI) to explore these changes in common shrews, revealing significant alterations in water diffusion properties such as increased mean diffusivity and decreased fractional anisotropy, leading to decreased water content inside brain cells during winter. These findings confirm that brain-size reduction correlates with a decrease in cell size, as our data indicate no reduction in cell numbers, showcasing a reorganization of brain tissue that supports survival without compromising brain function. These findings extend our understanding of neuronal resilience and may inform future research on regenerative mechanisms, particularly during the spring regrowth phase, offering potential strategies relevant to neurodegenerative disease.

Contrasting almost all other mammalian wintering strategies, Eurasian common shrews, Sorex araneus, endure winter by shrinking their brain, skull, and most organs, only to then regrow to breeding size the following spring. How such tiny mammals achieve this unique brain size plasticity while maintaining activity through the winter remains unknown. To discover potential adaptations underlying this trait, we analyzed seasonal differential gene expression in the shrew hypothalamus, a brain region that both regulates metabolic homeostasis and drastically changes size, and compared hypothalamus gene expression across species. We discovered seasonal variation in suites of genes involved in energy homeostasis and apoptosis, shrew-specific upregulation of genes involved in the development of the hypothalamic blood-brain barrier and calcium signaling, as well as overlapping seasonal and comparative gene expression divergence in genes implicated in the development and progression of human neurological and metabolic disorders, including CCDC22. With high metabolic rates and facing harsh winter conditions, S. araneus have evolved both adaptive and plastic mechanisms to sense and regulate their energy budget. Many of these changes mirrored those identified in human neurological and metabolic disease, highlighting the interactions between metabolic homeostasis, brain size plasticity, and longevity.

Winters are challenging environmental periods, consisting of decreased temperature and nutrient limitations. The Eurasian common shrew, …