Abstract
Estrogens, such as the biologically active 17-β estradiol (E2), regulate not only reproductive behaviors in adults, but also influence neurodevelopment and neuroprotection in both females and males. E2, contingent upon the timing and concentration of the therapy, is neuroprotective in female and male rodent models of stroke. In Vivo studies suggest that E2 may partially mediate this neuroprotection, particularly in the cortex, via ERα. In Vitro studies, utilizing a chemically induced ischemic injury in cortical explants from both sexes, suggest that ERα or ERβ signaling is needed to mediate the E2 protection. Since we know that the timing and concentration of E2 therapy may be sex-specific, we examined if E2 (1 nM) mediates neuroprotection when female and male cortical explants are separately isolated from postnatal day (PND) 3–4 rat. Changes in basal levels ERα, ERβ, and AR mRNA expression are compared across early post-natal development in the intact cortex and the corresponding days in vitro (DIV) for cortical explants. Following ischemic injury at 7 DIV, cell death and ERα, ERβ and AR mRNA expression was compared in female and male cortical explants. We provide evidence that E2-mediated protection is maintained in isolated cortical explants from females, but not male rats. In female cortical explants, the E2-mediated protection at 24 h occurs secondarily to a blunted transient increase in ERα mRNA at 12 h. These results suggest that cortical E2-mediated protection is influenced by sex and supports data to differentially treat females and males following ischemic injury.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.nbas.2024.100117
Funding Information
This work was funded by the National Science Foundation IOS1121129. Author (AT) was supported by an American Heart Association (AHA) Career Development Award (23CDA1054938) and by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) (KL2TR001996). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHA or NIH.
Repository Citation
Trout, Amanda L.; McLouth, Christopher J.; Westberry, Jenna; Sengoku, Tomoko; and Wilson, Melinda E., "Estrogen’s sex-specific effects on ischemic cell death and estrogen receptor mRNA expression in rat cortical organotypic explants" (2024). Neurology Faculty Publications. 120.
https://uknowledge.uky.edu/neurology_facpub/120
Notes/Citation Information
2589-9589/© 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).