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Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells

1
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Department of Biological Chemistry, Medical Pharmaceutical and Toxicological Chemistry, Partizan Zheleznyak st. 1, 660022 Krasnoyarsk, Russia
2
Siberian Federal University, Svobodny pr., 79, 660041 Krasnoyarsk, Russia
3
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Research Institute of Molecular Medicine and Pathobiochemistry, Partizan Zheleznyak st. 1, 660022 Krasnoyarsk, Russia
4
Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Partizan Zheleznyak st., 3G, 660022 Krasnoyarsk, Russia
5
Institute of Living Systems, Immanuel Kant Baltic Federal University, Universitetskaya st., 2, 236041 Kaliningrad, Russia
*
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(4), 80; https://doi.org/10.3390/brainsci9040080
Received: 29 March 2019 / Revised: 8 April 2019 / Accepted: 10 April 2019 / Published: 12 April 2019
(This article belongs to the Section Neuroglia)
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. View Full-Text
Keywords: astrocytes; S100β; Purkinje cells; short-term plasticity; Ca2+ signaling astrocytes; S100β; Purkinje cells; short-term plasticity; Ca2+ signaling
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Belozor, O.S.; Yakovleva, D.A.; Potapenko, I.V.; Shuvaev, A.N.; Smolnikova, M.V.; Vasilev, A.; Pozhilenkova, E.A.; Shuvaev, A.N. Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells. Brain Sci. 2019, 9, 80.

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