Elsevier

Experimental Neurology

Volume 143, Issue 2, February 1997, Pages 313-318
Experimental Neurology

Brief Communication
Astrocytes and Microglia Respond to Estrogen with Increased apoE mRNAin Vivoandin Vitro

https://doi.org/10.1006/exnr.1996.6360Get rights and content

Abstract

This study examined the regulation of apolipoprotein E (apoE) by 17β-estradiol (E2) in brain glia, using rats with regular ovulatory cycles as anin vivomodel and cultured astrocytes and mixed glia asin vitromodels. Two brain regions were examined which had demonstrated transient synaptic remodeling during the estrous cycle. In the hippocampal CA1 region and the hypothalamic arcuate nucleus, apoE mRNA was elevated at proestrus when plasma E2 was high and synaptic density was increasing. Both astrocytes and microglia contributed to this increase in apoE mRNA.In vitro,E2 treatment had no effect on apoE mRNA levels in monotypic cultures of either astrocytes or microglia. In contrast, mixed glial cultures responded to E2 with increased apoE mRNA and protein, suggesting that heterotypic cellular interactions are important in the brain response to estrogens.In situhybridization in combination with cell-specific markers showed that E2 increased apoE mRNA levels in both astrocytes and microglia. These results, which are the first evidence of apoE mRNA localization to microgliain vivoand the control of apoE expression in brain cells by estrogens, are discussed in terms of the possible protective role of E2 in Alzheimer's disease and prior findings that emphasize the expression of apoE mRNA in astrocytes within the brain.

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      Investigators have only begun to scratch the surface of why this might be the case. Some evidence suggests that APOE expression is impacted by estradiol (Lambert et al., 2004; Levin-Allerhand et al., 2001; Srivastava et al., 2008; Stone et al., 1997; Struble et al., 2003). In this age of enormous AD GWAS meta-analyses, the role of the X chromosome variants remains essentially unexplored (note that the Manhattan plots in all the large AD GWAS papers only show chromosomes 1–22) (Lambert et al., 2013; Marioni et al., 2018).

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    E. Knobil, Eds.J. D. Neill, Eds.

    1

    Both authors contributed equally and share first authorship.

    2

    To whom correspondence and reprint requests should be addressed. Fax: (213) 740-0853.

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