Extragonadal synthesis of estradiol is protective against kainic acid excitotoxic damage to the hippocampus.
Gonadal or exogenous estradiol is neuroprotective in multiple experimental paradigms. The role exerted by endogenous extragonadal estradiol synthesis in neuroprotection, however, is poorly understood. Here we show that a dose of kainic acid (3 mg/kg body weight) that does not produce detectable neuronal damage in control male and female gonadectomized rats induces a significant loss of hippocampal hilar neurons after the systemic inhibition of aromatase, the enzyme involved in estradiol biosynthesis from androgens. Extragonadal aromatase inhibition exerts a similar neuronal loss in both male and female rats (26% and 30% reduction in the number of hilar neurons, respectively). These findings indicate that extragonadal estradiol exerts a neuroprotective effect in both sexes, which prevents neuronal loss as a consequence of mild neurodegenerative signals.
Veiga
Sergio
S
Instituto Cajal, Consejo Superior de Investigaciones Científicas, Spain.
Azcoitia
Iñigo
I
Garcia-Segura
Luis M
LM
D000818:Animals; D002369:Castration / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
D004965:Estrogen Antagonists; D009478:Neuropeptide Y; D009498:Neurotoxins; D004958:Estradiol; D017316:Fadrozole; D007608:Kainic Acid