Estrogen receptors increased expression during hippocampal neuroprotection in lactating rats

Estrogen receptor (ER)-mediated neuroprotection has been demonstrated in both in vitro and in vivo model systems. Two types of estrogen receptors, ERalpha and ERbeta, are the major mediators of the biological functions of estrogens. In the hippocampus, ERbeta is prevalent over ERalpha. Recently, we reported that during the final phase of lactation there is a neuroprotective mechanism in the hippocampus of the adult female rat against neuronal damage induced by systemic kainic acid administration vs. virgin (metestrus) rats. In this study, we assessed differential ER expression and localization in CA1, CA3 and dentate gyrus regions of dorsal hippocampus of metestrus and lactating adult rats at day 19 of lactation, during basal conditions (metestrus and L19, respectively) and 24h after systemic kainate administration. ERs were assessed by western blot and immunohistochemistry. We found a significant increase in the expression of ERs in the hippocampus during lactation as compared with metestrus. ERbeta was significantly increased in the CA1 and CA3 of lactating rats after the kainic acid insult. In addition, we observed a relocalization of ERbeta from the cytoplasm to the nucleus of neuronal cells. Our results suggest that there is a strong correlation between expression of ERs, especially ERbeta, in lactating CA1 and CA3 hippocampus regions in response to kainate administration, and neuroprotection observed during this reproductive period. This may be one of the mechanisms involved in the protection of the maternal brain to ensure offspring survival.