Abstract：
:Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump α2-Na/K ATPase cause familial hemiplegic migraine, but the mechanisms by which α2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we show that mice in which α2-Na/K ATPase is conditionally deleted in astrocytes display episodic paralysis. Functional neuroimaging reveals that conditional α2-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 α2-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 α2-Na/K ATPase knockout mice. Together, our findings define a metabolic mechanism regulated by astrocytic α2-Na/K ATPase that triggers episodic motor paralysis in mice.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Smith SE,Chen X,Brier LM,Bumstead JR,Rensing NR,Ringel AE,Shin H,Oldenborg A,Crowley JR,Bice AR,Dikranian K,Ippolito JE,Haigis MC,Papouin T,Zhao G,Wong M,Culver JP,Bonni Adoi
10.1038/s41467-020-19915-2subject
Has Abstractpub_date
2020-12-02 00:00:00pages
6164issue
1issn
2041-1723pii
10.1038/s41467-020-19915-2journal_volume
11pub_type
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