Hormonal regulation of atypical absence seizures

Abstract

A time course study that examined the effects of the female estrous cycle on the chronic slow spike-and-wave discharges (SSWDs), gamma-aminobutyric B receptor (GABA(B)R) binding, and GABA(B)R protein expression was conducted in Long Evans hooded rats treated during development with a cholesterol synthesis inhibitor AY9944 (AY). In addition, a pharmacological study using the hormones progesterone, 17 beta-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 there is a significant increase in both the duration of SSWD and GABA(B)R 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 GABA(B)R1a or R2 protein levels were observed. In addition, the administration of both progesterone and allopregnanolone exacerbated seizures in the AY model, whereas 17 beta-estradiol attenuated the SSWD duration. Neither mifepristone nor tamoxifen blocked the effects of progesterone and 17 beta-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.

Progesterone: the forgotten hormone in men?

“…Chronic slow spikeand-wave discharges (SSWDs) induced by the cholesterol synthesis inhibitor AY9944 in Long Evans rats were exacerbated by the administration of both progesterone and allopregnanolone. This effect was not blocked by mifepristone 141 .…”

The role of ovarian steroid hormones in the regulation of basal and stress induced absence seizures

“…Virtually, a number of adaptive changes in specific binding associated with GABA A receptors as well as in density of dopamine receptors was indeed observed following ovariectomy in different brain structures such as striatum and prefrontal cortex [24,25]. The lack of any changes in the basal occurrence of SWDs in OVX females raises doubts whether and in which way ovarian steroids play a role in the regulation of SWDs under resting conditions [5][6][7][8].…”

“…It has been demonstrated that acute administration of progesterone aggravates the number of absence seizures both in humans [4] and in rats [5][6][7]. It was also shown that this effect is mediated by the neuroactive derivative allopregnanolone known to facilitate GABA A receptor inhibitory function [6].…”

Gender issues in the neurobiology of epilepsy: A clinical perspective

“…Epilepsy syndromes in general can also be influenced by hormonal background (Persad et al, 2004). Certain syndromes such as juvenile myoclonic epilepsy, generalized tonic clonic activity on waking, benign rolandic epilepsy, photosensitive epilepsy, reading epilepsy and some generalized epilepsy syndromes present during adolescence (or menarche in girls), when levels of sex hormones rise due to puberty (Grϋnewald et al, 1992;Velišková et al, 2010;Velišková and Desantis, 2013).…”