Neuroprotective effects of estrone on NMDA-induced toxicity in primary cultures of rat cortical neurons are independent of estrogen receptors.
It has been hypothesized that some estrogenic metabolites with low hormonal activity, such as estrone or estriol, may serve as endogenous neuroprotective agents. Since estrone naturally occurs in abundance in the human brain, we evaluated its effects on the NMDA-induced toxicity in primary cultures of the rat cortical neurons. The results showed that NMDA (1 mM) had toxic effect on the rat cortical neurons on 12, but not on 7 day in vitro. This effect was partially prevented by DL-2-amino-5-phosphonovaleric acid (AP-5); a competetive NMDA receptor antagonist. Estrone (500 nM) attenuated the NMDA-induced toxicity in estrogen receptor-independent way. These data support the hypothesis that toxic effects of NMDA depend on stage of neuronal development and point to non-genomic neuroprotective actions of estradiol metabolites.
Kajta
Małgorzata
M
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. malgorzata.kajta@medizin.uni-ulm.de
Lasoń
Władysław
W
Bień
Ewa
E
Marszał
Michał
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004970:Estrone / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000502:physiology*
D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D004970:Estrone; D016202:N-Methylaspartate