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

Cynthia Bethea, Steven Kohama, Arubala Reddy, Henryk Urbanski

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    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
    Volume37
    DOIs
    StatePublished - Jan 1 2016

    Fingerprint

    Macaca
    Steroids
    Gene Expression
    Hormones
    Menopause
    Synaptic Transmission
    Neurodegenerative Diseases
    Genes
    Estradiol
    Depression
    Metabolic Diseases
    Macaca mulatta
    Reverse Transcriptase Polymerase Chain Reaction
    DNA Repair
    Synapses
    Cognition
    Osteoporosis
    Weight Gain
    Progesterone
    Glutamic Acid

    Keywords

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

    ASJC Scopus subject areas

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

    Cite this

    Ovarian steroids regulate gene expression in the dorsal raphe of old female macaques. / Bethea, Cynthia; Kohama, Steven; Reddy, Arubala; Urbanski, Henryk.

    In: Neurobiology of Aging, Vol. 37, 01.01.2016, p. 179-191.

    Research output: Contribution to journalArticle

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