2 research outputs found
Extracellular S100Ξ² 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.
S100Ξ² is a Ca 2+ binding protein. In SCA1, excessive excretion of S100Ξ² by reactive astrocytes and its
uptake by Purkinje cells has been demonstrated previously. Under pathological conditions, excessive
extracellular concentration of S100Ξ² stimulates the production of proinflammatory cytokines and
induces apoptosis. We modeled astrogliosis by S100Ξ² injections into cerebellar cortex in mice.
Injections of S100Ξ² led to significant changes in Bergmann glia (BG) cortical organization and
affected their processes. S100Ξ² 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 S100Ξ² injections.
We speculate that these effects are the result of Ca 2+ -chelating properties of S100Ξ² protein. In summary,
exogenous S100Ξ² 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 S100Ξ² is an important contributor to this process
Extracellular S100Ξ² 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. S100β is a Ca2+ binding protein. In SCA1, excessive excretion of S100β by reactive astrocytes and its uptake by Purkinje cells has been demonstrated previously. Under pathological conditions, excessive extracellular concentration of S100β stimulates the production of proinflammatory cytokines and induces apoptosis. We modeled astrogliosis by S100β injections into cerebellar cortex in mice. Injections of S100β led to significant changes in Bergmann glia (BG) cortical organization and affected their processes. S100β 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 S100β injections. We speculate that these effects are the result of Ca2+-chelating properties of S100β protein. In summary, exogenous S100β 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 S100β is an important contributor to this process