Ovarian steroids regulate gene expression in the dorsal raphe of old female macaques

Cynthia L. Bethea, Steven G. Kohama, Arubala P. Reddy, Henryk F. Urbanski

    Research output: Contribution to journalArticlepeer-review

    14 Scopus citations


    With extended life spans in modern humans, menopause has become a significant risk factor for depression, anxiety, loss of cognitive functions, weight gain, metabolic disease, osteoporosis, cardiovascular disease, and neurodegenerative diseases. Clinical studies have found beneficial neural effects of ovarian steroid hormone therapy (HT) during the menopausal transition and data are emerging that it can be continued long term. To further understand molecular underpinnings of the clinical studies, we used quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to examine gene expression in the serotonergic dorsal raphe of old (>18 years) rhesus macaques, focusing on genes related to depression, cellular resilience, and neurodegenerative diseases. The animals were ovariectomized (Ovx, surgically menopausal) and subjected to either estradiol or estradiol plus progesterone HT, or to placebo, starting 2 months after Ovx and continuing for ∼4 years. Significant changes were observed in 36 of 48 genes examined that encode proteins supporting serotonin neurotransmission, synapse assembly, glutamate neurotransmission, DNA repair, chaperones, ubiquinases and transport motors, as well as genes encoding proteins that have potential to delay the onset of neuropathologies. The data reveal important gene targets for chronic HT that contribute to neural health. Alternatively, the loss of ovarian steroids may lead to loss of functions at the gene level that contribute to many of the observable neural deficits after menopause.

    Original languageEnglish (US)
    Pages (from-to)179-191
    Number of pages13
    JournalNeurobiology of Aging
    StatePublished - Jan 1 2016


    • Chaperones
    • DNA repair
    • Dorsal raphe
    • Estrogen
    • Glutamate
    • Macaques
    • Neurodegeneration
    • Progesterone
    • Serotonin
    • Synapse
    • Transport
    • Ubiquinases

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Aging
    • Clinical Neurology
    • Developmental Biology
    • Geriatrics and Gerontology


    Dive into the research topics of 'Ovarian steroids regulate gene expression in the dorsal raphe of old female macaques'. Together they form a unique fingerprint.

    Cite this