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Non-genomic Effect of Estradiol on the Neurovascular Unit and Possible Involvement in the Cerebral Vascular Accident

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Abstract

Cerebrovascular diseases, such as ischemic cerebral vascular accident (CVA), are responsible for causing high rates of morbidity, mortality, and disability in the population. The neurovascular unit (NVU) during and after ischemic CVA plays crucial roles in cell regulation and preservation, the immune and inflammatory response, and cell and/or tissue survival and repair. Cellular responses to 17β-estradiol (E2) can be triggered by two mechanisms: one called classical or genomic, which is due to the activation of the “classical” nuclear estrogen receptors α (ERα) and β (ERβ), and the non-genomic or rapid mechanism, which is due to the activation of the G protein–coupled estrogen receptor 1 (GPER) that is located in the plasma membrane and some in intracellular membranes, such as in the Golgi apparatus and endoplasmic reticulum. Nuclear receptors can regulate gene expression and cellular functions. On the contrary, activating the GPER by E2 and/or its G-1 agonist triggers several rapid cell signaling pathways. Therefore, E2 or its G-1 agonist, by mediating GPER activation and/or expression, can influence several NVU cell types. Most studies argue that the activation of the GPER may be used as a potential therapeutic target in various pathologies, such as CVA. Thus, with this review, we aimed to summarize the existing literature on the role of GPER mediated by E2 and/or its agonist G-1 in the physiology and pathophysiology of NVU.

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Funding

This work was supported by the Foundation for Science and Technology (FCT), through funds from the State Budget, and by the European Regional Development Fund (ERDF), under the Portugal 2020 Program, through the Regional Operational Program of the Center (Centro2020), and through the Projects with the references (UIDB/00709/2020 + UIDP/00709/2020). M.L. received the Ph.D. fellowship from FCT (Reference: 2020.06616.BD).

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  1. CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique S/N, 6200-506, Covilha, Portugal

    Francisca Jorge Gonçalves, Fatima Abrantes-Soares, Manuel R. Pouso, Margarida Lorigo & Elisa Cairrao

  2. FC-UBI - Faculty of Sciences, University of Beira Interior, 6201-001, Covilha, Portugal

    Francisca Jorge Gonçalves, Fatima Abrantes-Soares & Manuel R. Pouso

  3. FCS-UBI – Faculty of Health Sciences, University of Beira Interior, 6200-506, Covilha, Portugal

    Margarida Lorigo & Elisa Cairrao

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Francisca Jorge Gonçalves: investigation; writing — original draft; writing — review and editing. Fatima Abrantes-Soares: writing — original draft; writing — review and editing. Manuel R Pouso: validation; writing — original draft; writing — review and editing. Margarida Lorigo: validation; writing — original draft; writing — review and editing. Elisa Cairrao: conceptualization; validation; funding acquisition; project administration; supervision; writing — review and editing. All authors read and approved the final manuscript.

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Gonçalves, F.J., Abrantes-Soares, F., Pouso, M.R. et al. Non-genomic Effect of Estradiol on the Neurovascular Unit and Possible Involvement in the Cerebral Vascular Accident. Mol Neurobiol 60, 1964–1985 (2023). https://doi.org/10.1007/s12035-022-03178-7

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