| First Author | Smith SE | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 6164 |
| PubMed ID | 33268780 | Mgi Jnum | J:299907 |
| Mgi Id | MGI:6490806 | Doi | 10.1038/s41467-020-19915-2 |
| Citation | Smith SE, et al. (2020) Astrocyte deletion of alpha2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway. Nat Commun 11(1):6164 |
| abstractText | Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump alpha2-Na/K ATPase cause familial hemiplegic migraine, but the mechanisms by which alpha2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we show that mice in which alpha2-Na/K ATPase is conditionally deleted in astrocytes display episodic paralysis. Functional neuroimaging reveals that conditional alpha2-Na/K ATPase knockout triggers spontaneous cortical spreading depression events that are associated with EEG low voltage activity events, which correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that alpha2-Na/K ATPase loss alters metabolic gene expression with consequent serine and glycine elevation in the brain. A serine- and glycine-free diet rescues the transient motor impairment in conditional alpha2-Na/K ATPase knockout mice. Together, our findings define a metabolic mechanism regulated by astrocytic alpha2-Na/K ATPase that triggers episodic motor paralysis in mice. |
