Estrone, but not 17 beta-estradiol, attenuates kainate-induced seizures and toxicity in mate mice

Estrogens change the susceptibility to seizures in humans and experimental animals. In this study, the effect of estrone and 17 beta -estradiol on kai nate-induced seizures and neurotoxicity was investigated in male mice. Pre- treatment with estrone (250-1000 mug/kg) at 24 and 2 hours before kainate ( 40 mg/kg) administration significantly decreased both the percentage of ani mals with clonic seizures and their mortality (thr latter at a dose of 1000 mug/kg only). On the other hand, 17 beta -estradiol (10-500 mug/ kg) had n o effect on seizures: and its dose of 10 mug/kg increased mortality. When g iven alone at a dose of 1 mg/kg, tamoxifen, an antagonist at estrogene rece ptors, did not affect the kainate-induced seizures, but prevented the antic onvulsant effect of estrone. A histological analysis showed that 73% of mic e injected with vehiculum and kainate incurred hippocampal damage. Estrone (2000 mug/kg) decreased the percentage of animals with hippocampal neuronal loss down to 43%, and that effect was not antagonized by tamoxifen. Pretre atment of mice with 17 beta -estradiol had no effect on the kainate-induced neuronal loss. Additionally, we found that kainate injected i.p. had a pro found effect on the immune system of mice, as reflected by a decrease in th e thymus weight and an increased metabolic activity of splenocytes. The ant iconvulsive dose of estrone (1000 mug/kg) did not change the immunoreactivi ty of either control or kainate-treated mice. In conclusion, the obtained d ata indicate that estrone, but not 17 beta -estradiol, attenuates the kaina te-induced seizures, mortality and excitotoxicity in male mice. Moreover, i t is suggested that the suppressive effect of estrone on clonic seizures in volves intracellular receptors, whereas its antineurotoxic activity seems t o depend on a non-genomic mechanism.