Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo
| العنوان: | Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo |
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| المؤلفون: | Brandon Brown, Fadi A. Issa, Brittany Ulrich, Diane M. Papazian, Meng-chin A. Lin, Jui-Yi Hsieh |
| المصدر: | eLife, Vol 9 (2020) eLife |
| بيانات النشر: | eLife Sciences Publications, Ltd, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cerebellum, Programmed cell death, cerebellum, Cell Survival, QH301-705.5, Science, Purkinje cell, Synaptogenesis, degeneration, General Biochemistry, Genetics and Molecular Biology, Purkinje Cells, 03 medical and health sciences, spinocerebellar ataxia, 0302 clinical medicine, In vivo, excitability, medicine, Cerebellar Degeneration, Animals, Spinocerebellar Ataxias, Biology (General), Zebrafish, General Immunology and Microbiology, biology, General Neuroscience, Age Factors, General Medicine, Zebrafish Proteins, medicine.disease, biology.organism_classification, Cell biology, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Shaw Potassium Channels, cerebellar development, Mutation, Spinocerebellar ataxia, Medicine, 030217 neurology & neurosurgery, Research Article, Neuroscience |
| الوصف: | Mutations in KCNC3, which encodes the Kv3.3 K+ channel, cause spinocerebellar ataxia 13 (SCA13). SCA13 exists in distinct forms with onset in infancy or adulthood. Using zebrafish, we tested the hypothesis that infant- and adult-onset mutations differentially affect the excitability and viability of Purkinje cells in vivo during cerebellar development. An infant-onset mutation dramatically and transiently increased Purkinje cell excitability, stunted process extension, impaired dendritic branching and synaptogenesis, and caused rapid cell death during cerebellar development. Reducing excitability increased early Purkinje cell survival. In contrast, an adult-onset mutation did not significantly alter basal tonic firing in Purkinje cells, but reduced excitability during evoked high frequency spiking. Purkinje cells expressing the adult-onset mutation matured normally and did not degenerate during cerebellar development. Our results suggest that differential changes in the excitability of cerebellar neurons contribute to the distinct ages of onset and timing of cerebellar degeneration in infant- and adult-onset SCA13. |
| تدمد: | 2050-084X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbeb67baefda06e2cb741c98f7bf4087 https://doi.org/10.7554/elife.57358 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cbeb67baefda06e2cb741c98f7bf4087 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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