Androgenic Suppression of Spreading Depression in Familial Hemiplegic Migraine Type 1 Mutant Mice

Overview

Journal Ann Neurol

Specialty Neurology

Date 2009 Oct 23

PMID 19847904

Citations 50

Authors

Katharina Eikermann-Haerter

Michael J Baum

Michel D Ferrari

Arn M J M van den Maagdenberg

Michael A Moskowitz

Cenk Ayata

Affiliations

Soon will be listed here.

Abstract

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.

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