JCI - Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I. Savitz, Christian Waeber, Michael J. Baum, Michel D. Ferrari, Arn M.J.M. van den Maagdenberg, Michael A. Moskowitz, Cenk Ayata

Published in Volume 119, Issue 1

J Clin Invest. 2009; 119(1):99–109 doi:10.1172/JCI36059

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Figure 3

Prolonged and severe neurological deficits after SD in FHM1 mutant mice.

Time course of neurological deficits in WT and FHM1 mutant mice after a single SD (A) or 9 SDs over 1 hour (B), as assessed by wire grip score and latency as well as neurological score. (A) Impact of allelic mutations and allele dosage. In WT mice, deficits were mild and short-lasting in wire grip test and undetectable by neurological scoring (triangles). FHM1 mutants developed severe and prolonged deficits (P < 0.01 versus WT). These deficits were markedly more severe and prolonged in homozygous S218L (black circles) than in homozygous R192Q mutants (gray circles; P < 0.01) or heterozygous S218L mutants (squares; P < 0.01 in wire grip test, P < 0.05 in neurological scoring). n = 13, 7, 6, and 3 WT, homozygous R192Q, heterozygous S218L, and homozygous S218L mutant mice, respectively. (B) Sex differences. In WT mice, deficits were mild and completely recovered within 45 minutes after 9 SDs. In contrast, R192Q mutant mice developed severe and prolonged deficits that lasted 80 minutes or more after 9 SDs (P < 0.01 versus WT). Importantly, female mutant mice (circles) were more severely affected than males (squares; P < 0.01). Deficits did not differ between WT males and females; therefore, data were pooled (triangles). n = 15, 6, and 7 WT, male R192Q, and female R192Q mutant mice, respectively. Error bars were omitted for clarity but were less than 25% of mean.