Cerebellar spreading depolarization mediates paroxysmal movement disorder
| Autor: | Sen-Sen Lou, Jing Zhang, Bin Lu, Rong-Jie Wu, Ruo-Shui Xu, Zhi-Ying Wu, Jun-Yan He, Ling Zhuang, Zhi-Qi Xiong, Xue-Mei Wu, De-Lun Kong |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cerebellum Patch-Clamp Techniques QH301-705.5 Purkinje cell Action Potentials Nav channel Voltage-Gated Sodium Channels cerebellar granule cell In Vitro Techniques Deep cerebellar nuclei General Biochemistry Genetics and Molecular Biology Potassium Chloride Mice Purkinje Cells spreading depolarization medicine otorhinolaryngologic diseases Animals inactivation Biology (General) Dystonia Mice Knockout Neurons Voltage-Gated Sodium Channel Blockers business.industry Membrane Proteins Depolarization Paroxysmal dyskinesia medicine.disease Mice Inbred C57BL Electrophysiology medicine.anatomical_structure nervous system PRRT2 Calcium Electrocorticography business Neuroscience |
| Zdroj: | Cell Reports, Vol 36, Iss 12, Pp 109743-(2021) |
| ISSN: | 2211-1247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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