Abstract

Hormonal Regulation of Absence SeizuresPersad V, Ting Wong CG, Cortez MA, Wang YT, Snead OC 3rdAnn Neurol 2004;44:353–361A time course study that examined the effects of the female estrous cycle on the chronic slow spike-and-wave discharges (SSWDs), GABAB-receptor (GABABR) binding, and GABABR protein expression was conducted in Long-Evans hooded rats treated during development with a cholesterol synthesis inhibitor AY9944 (AY). In addition, a pharmacologic study using the hormones progesterone, 17 β-estradiol, mifepristone (intracellular progesterone-receptor antagonist), tamoxifen (intracellular estrogen-receptor antagonist), and allopregnanolone (progesterone metabolite) was performed to determine their effects on AY-induced seizures. The data indicate that a significant increase occurs in both the duration of SSWDs and GABABR binding in the AY model during the proestrus stage of the estrous cycle, the stage during which the levels of progesterone are at their highest. No changes in GABABR1a or R2 protein levels were observed. In addition, the administration of both progesterone and allopregnanolone exacerbated seizures in the AY model, whereas 17 β-estradiol attenuated the SSWD duration. Neither mifepristone nor tamoxifen blocked the effects of progesterone and 17 β-estradiol, respectively, on SSWD duration in the AY model, suggesting that these two sex hormones are working in a manner independent of their intracellular receptors. These data suggest an important role for steroid hormones in the regulation and maintenance of AY-induced atypical absence seizures.

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