title: Extragonadal synthesis of estradiol is protective against kainic acid excitotoxic damage to the hippocampus.
abstract: 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.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Veiga
authors.forename: Iñigo
authors.initials: I
authors.lastname: Azcoitia
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
mesh_terms: 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
chemical_list: D004965:Estrogen Antagonists; D009478:Neuropeptide Y; D009498:Neurotoxins; D004958:Estradiol; D017316:Fadrozole; D007608:Kainic Acid