Targeting Na,K-ATPase-Src signaling to normalize cerebral blood flow in a murine model of familial hemiplegic migraine.

ABSTRACT: Familial hemiplegic migraine type 2 (FHM2) is linked to Na,K-ATPase α₂ isoform mutations, including that of G301R. Mice heterozygous for this mutation (α2+/G301R) show cerebrovascular hypercontractility associated with amplified Src kinase signaling, and exaggerated neurovascular coupling. This study hypothesized that targeting Na,K-ATPase-dependent Src phosphorylation with pNaKtide would normalize cerebral perfusion and neurovascular coupling in α2+/G301R mice. The effect of pNaKtide on cerebral blood flow and neurovascular coupling was assessed using laser speckle contrast imaging in awake, head-fixed mice with cranial windows in a longitudinal study design. At baseline, compared to wild type, α2+/G301R mice exhibited increased middle cerebral artery tone; with whisker stimula

SUBMITTER: Staehr C 

PROVIDER: S-EPMC11615910 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature