ASTROCYTES AND MICROGLIA RESPOND TO ESTROGEN WITH INCREASED APOE MESSENGER-RNA IN-VIVO AND IN-VITRO

This study examined the regulation of apolipoprotein E (apoE) by 17 be ta-estradiol (E2) in brain glia, using rats with regular ovulatory cyc les as an in vivo model and cultured astrocytes and mixed glia as in v itro models. Two brain regions were examined which had demonstrated tr ansient synaptic remodeling during the estrous cycle. In the hippocamp al CA1 region and the hypothalamic arcuate nucleus, apoE mRNA was elev ated at proestrus when plasma E2 was high and synaptic density was inc reasing. Both astrocytes and microglia contributed to this increase in apoE mRNA. In vitro, E2 treatment had no effect on apoE mRNA levels i n monotypic cultures of either astrocytes or microglia. In contrast, m ixed glial cultures responded to E2 with increased apoE mRNA and prote in, suggesting that heterotypic cellular interactions are important in the brain response to estrogens. In situ hybridization in combination with cell-specific markers showed that E2 increased apoE mRNA levels in both astrocytes and microglia. These results, which are the first e vidence of apoE mRNA localization to microglia in vivo and the control of apoE expression in brain cells by estrogens, are discussed in term s of the possible protective role of E2 in Alzheimer's disease and pri or findings that emphasize the expression of apoE mRNA in astrocytes w ithin the brain. (C) 1997 Academic Press.