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Modulation of neural gene networks by estradiol in old rhesus macaque females.
Cervera-Juanes, Rita; Zimmerman, Kip D; Wilhelm, Larry; Zhu, Dongqin; Bodie, Jessica; Kohama, Steven G; Urbanski, Henryk F.
Afiliación
  • Cervera-Juanes R; Department of Translational Neuroscience, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
  • Zimmerman KD; Center for Precision Medicine, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
  • Wilhelm L; Center for Precision Medicine, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
  • Zhu D; Department of Internal Medicine, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
  • Bodie J; Department of Translational Neuroscience, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
  • Kohama SG; Department of Translational Neuroscience, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
  • Urbanski HF; Department of Translational Neuroscience, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157.
bioRxiv ; 2023 Dec 18.
Article en En | MEDLINE | ID: mdl-38187564
ABSTRACT
The postmenopausal decrease in circulating estradiol (E2) levels has been shown to contribute to several adverse physiological and psychiatric effects. To elucidate the molecular effects of E2 on the brain, we examined differential gene expression and DNA methylation (DNAm) patterns in the nonhuman primate brain following ovariectomy (Ov) and subsequent E2 treatment. We identified several dysregulated molecular networks, including MAPK signaling and dopaminergic synapse response, that are associated with ovariectomy and shared across two different brain areas, the occipital cortex (OC) and prefrontal cortex (PFC). The finding that hypomethylation (p=1.6×10-51) and upregulation (p=3.8×10-3) of UBE2M across both brain regions, provide strong evidence for molecular differences in the brain induced by E2 depletion. Additionally, differential expression (p=1.9×10-4; interaction p=3.5×10-2) of LTBR in the PFC, provides further support for the role E2 plays in the brain, by demonstrating that the regulation of some genes that are altered by ovariectomy may also be modulated by Ov followed by hormone replacement therapy (HRT). These results present real opportunities to understand the specific biological mechanisms that are altered with depleted E2. Given E2's potential role in cognitive decline and neuroinflammation, our findings could lead to the discovery of novel therapeutics to slow cognitive decline. Together, this work represents a major step towards understanding molecular changes in the brain that are caused by ovariectomy and how E2 treatment may revert or protect against the negative neuro-related consequences caused by a depletion in estrogen as women approach menopause.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos