Estrone, but not 17 beta-estradiol, attenuates kainate-induced seizures and toxicity in male mice.
Estrogens change the susceptibility to seizures in humans and experimental animals. In this study, the effect of estrone and 17 beta-estradiol on kainate-induced seizures and neurotoxicity was investigated in male mice. Pre-treatment with estrone (250-1000 micrograms/kg) at 24 and 2 hours before kainate (40 mg/kg) administration significantly decreased both the percentage of animals with clonic seizures and their mortality (the latter at a dose of 1000 micrograms/kg only). On the other hand, 17 beta-estradiol (10-500 micrograms/kg) had no effect on seizures, and its dose of 10 micrograms/kg increased mortality. When given alone at a dose of 1 mg/kg, tamoxifen, an antagonist at estrogene receptors, did not affect the kainate-induced seizures, but prevented the anticonvulsant effect of estrone. A histological analysis showed that 73% of mice injected with vehiculum and kainate incurred hippocampal damage. Estrone (2000 micrograms/kg) decreased the percentage of animals with hippocampal neuronal loss down to 43%, and that effect was not antagonized by tamoxifen. Pretreatment 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 profound effect on the immune system of mice, as reflected by a decrease in the thymus weight and an increased metabolic activity of splenocytes. The anticonvulsive dose of estrone (1000 micrograms/kg) did not change the immunoreactivity of either control or kainate-treated mice. In conclusion, the obtained data indicate that estrone, but not 17 beta-estradiol, attenuates the kainate-induced seizures, mortality and excitotoxicity in male mice. Moreover, it is suggested that the suppressive effect of estrone on clonic seizures involves intracellular receptors, whereas its antineurotoxic activity seems to depend on a non-genomic mechanism.
Budziszewska
B
B
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Leśkiewicz
M
M
Kubera
M
M
Jaworska-Feil
L
L
Kajta
M
M
Lasoń
W
W
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004970:Estrone / Q000008:administration & dosage / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects; D007109:Immunity / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control*; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology
D004965:Estrogen Antagonists; D013629:Tamoxifen; D004970:Estrone; D004958:Estradiol; D007608:Kainic Acid