[Abstract Title]. - Society for Neuroscience

Poster
248. Dystonia
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 248.7/U6
Topic: C.03.j. Dystonia
Support: NIH NS40470
Bachmann-Strauss Dystonia and Parkinson Foundation
NIH F32 052040
Title: Female gonadal hormones and paroxysmal dystonia in rocker mice
Authors: *H. A. JINNAH, T. L. SHIRLEY, M. C. TERZI, E. J. HESS;
Dept Neurol, Johns Hopkins Univ., Baltimore, MD
Abstract: Ion channel dysfunction is known to cause several forms of episodic neurological
disease in humans. Different mutations in CACNA1A, the pore-forming subunit of CaV2.1
calcium channels, underlie several distinct disorders that include familial hemiplegic migraine,
episodic ataxia type 2, spinocerebellar ataxia 6, epilepsy, and dystonia. Such phenotypic
diversity also occurs in mice carrying different mutations in Cacna1a (tottering, rolling mouse
Nagoya, leaner, rocker, and two knockouts). Intermittent dystonic attacks resembling
paroxysmal dyskinesia have only been described for tottering and rocker mice. The most
distinctive feature of attacks in rocker mice is their sexual dimorphism, with attacks occurring
almost exclusively in adult females. This sex difference could be due to the effects of gonadal
sex hormones on the central nervous system. Orchidectomy was performed in young male rocker
mice to determine whether gonadal androgens are suppressive, but this failed to induce attacks in
adult males. Conversely, ovariectomy in young female rocker eliminated attacks in adult females
suggesting that female gonadal hormones are required for dystonia attacks. Combining
ovariectomy with chronic estrogen (in the form of 17Β-estradiol) or progesterone replacement
using silastic tubing implants will be conducted to determine which gonadal hormone is required
for dystonia attacks. Cross-replacement in orchidectomized males will help determine whether
hormone alone is sufficient. Sex bias occurs in many prevalent human neurological diseases such
as migraine, epilepsy and dystonia. Rocker mice provide a model of sexually dimorphic
neurological dysfunction that could offer new insight into the mechanisms of sex hormone
modulation of disease.
Disclosures: H.A. Jinnah , None; T.L. Shirley, None; M.C. Terzi, None; E.J. Hess, None.