Differential role of gonadal hormones on kainic acid–induced neurodegeneration in medial amygdaloid nucleus of female and male rats

Abstract Sex hormones contribute to modulating brain functions throughout the life span. It has been suggested that estrogen prevents neuronal loss in different areas of the CNS such as the hippocampus. However there are less consistent data on its effects on the amygdala. Kainic acid (KA) is used to produce seizures that mimic those of temporal lobe epilepsy in humans. At high doses in animal models, KA induces neurotoxicity, particularly in the medial amygdaloid nuclei (MeA). It is uncertain whether the gonadal hormones are protective or not against this neurotoxicity in the MeA. Here we show that a single dose of KA induces neurodegeneration in the subnuclei of the MeA of rats with different degrees of intensity in males and females. A differential neuroprotective effect of the gonadal hormones was also observed. In diestrous rats, massive neuronal death similar to that in the ovariectomized females was detected. MeA neurons of proestrous rats, like the ovariectomized treated with estrogen, were significantly less affected by the KA. Testosterone produced a mild neuroprotective action, but dihydrotestosterone did not protect. A similar pattern was observed in all male groups. Together, the results indicate that estrogen protects MeA neurons from KA neurotoxicity. Androgens are only partially neuroprotective, with this effect being found only in testosterone, probably through its conversion to estrogen by aromatase.