Extracellular S100β 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...
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MDPI AG
2019-04-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/9/4/80 |
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| author | Olga S. Belozor Dariya A. Yakovleva Ilya V. Potapenko Andrey N. Shuvaev Marina V. Smolnikova Alex Vasilev Elena A. Pozhilenkova Anton N. Shuvaev |
| author_facet | Olga S. Belozor Dariya A. Yakovleva Ilya V. Potapenko Andrey N. Shuvaev Marina V. Smolnikova Alex Vasilev Elena A. Pozhilenkova Anton N. Shuvaev |
| author_sort | Olga S. Belozor |
| collection | DOAJ |
| description | 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>-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. |
| first_indexed | 2024-12-12T17:48:58Z |
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| issn | 2076-3425 |
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| last_indexed | 2024-12-12T17:48:58Z |
| publishDate | 2019-04-01 |
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| series | Brain Sciences |
| spelling | doaj.art-4a11e954e8ff4191b60cb24f5fbf85d12022-12-22T00:16:51ZengMDPI AGBrain Sciences2076-34252019-04-01948010.3390/brainsci9040080brainsci9040080Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje CellsOlga S. Belozor0Dariya A. Yakovleva1Ilya V. Potapenko2Andrey N. Shuvaev3Marina V. Smolnikova4Alex Vasilev5Elena A. Pozhilenkova6Anton N. Shuvaev7Krasnoyarsk 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, RussiaSiberian Federal University, Svobodny pr., 79, 660041 Krasnoyarsk, RussiaKrasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Research Institute of Molecular Medicine and Pathobiochemistry, Partizan Zheleznyak st. 1, 660022 Krasnoyarsk, RussiaSiberian Federal University, Svobodny pr., 79, 660041 Krasnoyarsk, RussiaKrasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Research Institute of Molecular Medicine and Pathobiochemistry, Partizan Zheleznyak st. 1, 660022 Krasnoyarsk, RussiaInstitute of Living Systems, Immanuel Kant Baltic Federal University, Universitetskaya st., 2, 236041 Kaliningrad, RussiaKrasnoyarsk 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, RussiaKrasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Research Institute of Molecular Medicine and Pathobiochemistry, Partizan Zheleznyak st. 1, 660022 Krasnoyarsk, RussiaAstrogliosis 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>-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.https://www.mdpi.com/2076-3425/9/4/80astrocytesS100βPurkinje cellsshort-term plasticityCa<sup>2+</sup> signaling |
| spellingShingle | Olga S. Belozor Dariya A. Yakovleva Ilya V. Potapenko Andrey N. Shuvaev Marina V. Smolnikova Alex Vasilev Elena A. Pozhilenkova Anton N. Shuvaev Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells Brain Sciences astrocytes S100β Purkinje cells short-term plasticity Ca<sup>2+</sup> signaling |
| title | Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells |
| title_full | Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells |
| title_fullStr | Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells |
| title_full_unstemmed | Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells |
| title_short | Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells |
| title_sort | extracellular s100β disrupts bergman glia morphology and synaptic transmission in cerebellar purkinje cells |
| topic | astrocytes S100β Purkinje cells short-term plasticity Ca<sup>2+</sup> signaling |
| url | https://www.mdpi.com/2076-3425/9/4/80 |
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