Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling.

ABSTRACT: In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during brain pathology remains unknown. Here we study the nanoscale organization of pathological ECS in adult mice under degenerative conditions. Using electron microscopy in cryofixed tissue and single nanotube tracking in live brain slices combined with super-resolution imaging analysis, we find enlarged ECS dimensions and increased nanoscale diffusion after α-synuclein-induced neurodegeneration. These animals display a degraded hyaluronan matrix in areas close to reactive microglia. Furthermore, experimental hyaluronan depletion in vivo reduces dopaminergic cell loss and α-synuclein load, induces mi

SUBMITTER: Soria FN 

PROVIDER: S-EPMC7351768 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature