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Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice†

  1. Katharina Eikermann-Haerter MD1,
  2. Michael J. Baum PhD2,
  3. Michel D. Ferrari MD3,
  4. Arn M.J.M. van den Maagdenberg PhD3,4,
  5. Michael A. Moskowitz MD1,
  6. Cenk Ayata MD1,4,*

Article first published online: 18 JUN 2009

DOI: 10.1002/ana.21779

Issue

Annals of Neurology

Annals of Neurology

Volume 66, Issue 4, pages 564–568, October 2009

Additional Information

How to Cite

Eikermann-Haerter, K., Baum, M. J., Ferrari, M. D., van den Maagdenberg, A. M., Moskowitz, M. A. and Ayata, C. (2009), Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Annals of Neurology, 66: 564–568. doi: 10.1002/ana.21779

Author Information

  1. 1

    Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA

  2. 2

    Stroke and Neurovascular Regulation Laboratory, Department of Biology, Boston University, Boston, MA

  3. 3

    Department of Neurology and Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

  4. 4

    Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA

*Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, 149 13th Street, Room 6403, Charlestown, MA 02129

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 8 OCT 2009
  2. Article first published online: 18 JUN 2009
  3. Accepted manuscript online: 18 JUN 2009 12:00AM EST
  4. Manuscript Accepted: 8 JUN 2009
  5. Manuscript Revised: 7 JUN 2009
  6. Manuscript Received: 19 FEB 2009

Funded by

  • Deutsche Forschungsgemeinschaft. Grant Number: Ha5085/1-1
  • National Institutes of Health. Grant Numbers: NS061505, NS35611
  • Netherlands Organization for Scientific Research. Grant Numbers: 903-52-291, Vici 918.56.602
  • EU “EUROHEAD”. Grant Number: LSHM-CT-2004-504837
  • Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI)

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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. Ann Neurol 2009;66:564–568

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