Gonadal hormones affect neuronal vulnerability to excitotoxin-induced degeneration

The role of endogenous gonadal secretions in neuroprotection has been asses sed in a model of hippocampal degeneration induced by the systemic administ ration of kainic acid to adult male and female rats. A low dose of kainic a cid (7 mg/Kg b.w.) induced a significant loss of hilar dentate neurons in c astrated males and did not affect hilar neurons in intact males. The effect of kainic acid on hilar neurons in female rats was different depending on the day of the estrous cycle in which the neurotoxin was administered; whil e no significant effect of kainic acid was observed when it was injected in the morning of estrus, there was a significant loss of hilar neurons when it was injected in the morning of proestrus as well as when it was injected into ovariectomized rats. Estradiol or estradiol plus progesterone prevent ed hilar neuronal loss when injected simultaneously with kainic acid in ova riectomized rat. Progesterone by itself did not prevent neuronal loss induc ed by kainic acid and estogen was only effective when it was injected eithe r 24 h before or simultaneously with kainic acid and not when it was inject ed 24 h after the administration of the toxin. These findings indicate that endogenous gonadal hormones protect hippocampal hilar neurons from excitot oxic degeneration. In addition, the timing of exposure to ovarian hormones and the natural fluctuation of ovarian hormones during the estrous cycle ma y influence the vulnerability of hilar neurons to excitotoxicity. These fin dings are relevant to possible modifications in neurodegenerative risk in h umans as endogenous levels of gonadal hormones change during the menstrual cycle and during aging.