Extracellular S100 Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells

Astrogliosis is a pathological process that affects the density, morphology, and function of astrocytes. It is a common feature of brain trauma, autoimmune diseases, and neurodegeneration including spinocerebellar ataxia type 1 (SCA1), a poorly understood neurodegenerative disease. S100 is a Ca2+ binding protein. In SCA1, excessive excretion of S100 by reactive astrocytes and its uptake by Purkinje cells has been demonstrated previously. Under pathological conditions, excessive extracellular concentration of S100 stimulates the production of proinflammatory cytokines and induces apoptosis. We modeled astrogliosis by S100 injections into cerebellar cortex in mice. Injections of S100 led to significant changes in Bergmann glia (BG) cortical organization and affected their processes. S100 also changed morphology of the Purkinje cells (PCs), causing a significant reduction in the dendritic length. Moreover, the short-term synaptic plasticity and depolarization-induced suppression of synaptic transmission were disrupted after S100 injections. We speculate that these effects are the result of Ca2+-chelating properties of S100 protein. In summary, exogenous S100 induced astrogliosis in cerebellum could lead to neuronal dysfunction, which resembles a natural neurodegenerative process. We suggest that astrocytes play an essential role in SCA1 pathology, and that astrocytic S100 is an important contributor to this process.