Cerebellar spreading depolarization mediates paroxysmal movement disorder
Summary: Paroxysmal kinesigenic dyskinesia (PKD) is the most common paroxysmal dyskinesia, characterized by recurrent episodes of involuntary movements provoked by sudden changes in movement. Proline-rich transmembrane protein 2 (PRRT2) has been identified as the major causative gene for PKD. Here,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721011967 |
| _version_ | 1819101324527009792 |
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| author | Bin Lu Sen-Sen Lou Ruo-Shui Xu De-Lun Kong Rong-Jie Wu Jing Zhang Ling Zhuang Xue-Mei Wu Jun-Yan He Zhi-Ying Wu Zhi-Qi Xiong |
| author_facet | Bin Lu Sen-Sen Lou Ruo-Shui Xu De-Lun Kong Rong-Jie Wu Jing Zhang Ling Zhuang Xue-Mei Wu Jun-Yan He Zhi-Ying Wu Zhi-Qi Xiong |
| author_sort | Bin Lu |
| collection | DOAJ |
| description | Summary: Paroxysmal kinesigenic dyskinesia (PKD) is the most common paroxysmal dyskinesia, characterized by recurrent episodes of involuntary movements provoked by sudden changes in movement. Proline-rich transmembrane protein 2 (PRRT2) has been identified as the major causative gene for PKD. Here, we report that PRRT2 deficiency facilitates the induction of cerebellar spreading depolarization (SD) and inhibition of cerebellar SD prevents the occurrence of dyskinetic movements. Using Ca2+ imaging, we show that cerebellar SD depolarizes a large population of cerebellar granule cells and Purkinje cells in Prrt2-deficient mice. Electrophysiological recordings further reveal that cerebellar SD blocks Purkinje cell spiking and disturbs neuronal firing of the deep cerebellar nuclei (DCN). The resultant aberrant firing patterns in DCN are tightly, temporally coupled to dyskinetic episodes in Prrt2-deficient mice. Cumulatively, our findings uncover a pivotal role of cerebellar SD in paroxysmal dyskinesia, providing a potent target for treating PRRT2-related paroxysmal disorders. |
| first_indexed | 2024-12-22T01:16:52Z |
| format | Article |
| id | doaj.art-59814c130bb5454c8662f36509a815d4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T01:16:52Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-59814c130bb5454c8662f36509a815d42022-12-21T18:43:50ZengElsevierCell Reports2211-12472021-09-013612109743Cerebellar spreading depolarization mediates paroxysmal movement disorderBin Lu0Sen-Sen Lou1Ruo-Shui Xu2De-Lun Kong3Rong-Jie Wu4Jing Zhang5Ling Zhuang6Xue-Mei Wu7Jun-Yan He8Zhi-Ying Wu9Zhi-Qi Xiong10Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Neurology and Research Center of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China; Corresponding authorSummary: Paroxysmal kinesigenic dyskinesia (PKD) is the most common paroxysmal dyskinesia, characterized by recurrent episodes of involuntary movements provoked by sudden changes in movement. Proline-rich transmembrane protein 2 (PRRT2) has been identified as the major causative gene for PKD. Here, we report that PRRT2 deficiency facilitates the induction of cerebellar spreading depolarization (SD) and inhibition of cerebellar SD prevents the occurrence of dyskinetic movements. Using Ca2+ imaging, we show that cerebellar SD depolarizes a large population of cerebellar granule cells and Purkinje cells in Prrt2-deficient mice. Electrophysiological recordings further reveal that cerebellar SD blocks Purkinje cell spiking and disturbs neuronal firing of the deep cerebellar nuclei (DCN). The resultant aberrant firing patterns in DCN are tightly, temporally coupled to dyskinetic episodes in Prrt2-deficient mice. Cumulatively, our findings uncover a pivotal role of cerebellar SD in paroxysmal dyskinesia, providing a potent target for treating PRRT2-related paroxysmal disorders.http://www.sciencedirect.com/science/article/pii/S2211124721011967spreading depolarizationPRRT2Nav channelinactivationcerebellumcerebellar granule cell |
| spellingShingle | Bin Lu Sen-Sen Lou Ruo-Shui Xu De-Lun Kong Rong-Jie Wu Jing Zhang Ling Zhuang Xue-Mei Wu Jun-Yan He Zhi-Ying Wu Zhi-Qi Xiong Cerebellar spreading depolarization mediates paroxysmal movement disorder Cell Reports spreading depolarization PRRT2 Nav channel inactivation cerebellum cerebellar granule cell |
| title | Cerebellar spreading depolarization mediates paroxysmal movement disorder |
| title_full | Cerebellar spreading depolarization mediates paroxysmal movement disorder |
| title_fullStr | Cerebellar spreading depolarization mediates paroxysmal movement disorder |
| title_full_unstemmed | Cerebellar spreading depolarization mediates paroxysmal movement disorder |
| title_short | Cerebellar spreading depolarization mediates paroxysmal movement disorder |
| title_sort | cerebellar spreading depolarization mediates paroxysmal movement disorder |
| topic | spreading depolarization PRRT2 Nav channel inactivation cerebellum cerebellar granule cell |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721011967 |
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