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Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice
Author(s) -
EikermannHaerter Katharina,
Baum Michael J.,
Ferrari Michel D.,
van den Maagdenberg Arn M.J.M.,
Moskowitz Michael A.,
Ayata Cenk
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21779
Subject(s) - familial hemiplegic migraine , cortical spreading depression , migraine , mutant , aura , migraine with aura , endocrinology , medicine , phenotype , mutation , genetics , neuroscience , biology , gene
Familial hemiplegic migraine type 1 (FHM1), a severe migraine with aura variant, is caused by mutations in the CACNA1A gene. Mutant mice carrying the FHM1 R192Q mutation exhibit increased propensity for cortical spreading depression (CSD), a propagating wave of neuroglial depolarization implicated in migraine aura. The CSD phenotype is stronger in female R192Q mutants and diminishes after ovariectomy. Here, we show that orchiectomy reciprocally increases CSD susceptibility in R192Q mutant mice. Chronic testosterone replacement restores CSD susceptibility by an androgen receptor‐dependent mechanism. Hence, androgens modulate genetically‐enhanced CSD susceptibility and may provide a novel prophylactic target for migraine. Ann Neurol 2009;66:564–568
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