Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques

Cynthia Bethea, Arubala Reddy

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Depression often accompanies the perimenopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDDs, such as Alzheimer's, Parkinson's, Huntington, amyotrophic lateral sclerosis). Serotonin dysfunction is frequently found in the different etiologies of depression. We have shown that ovariectomized (Ovx) monkeys treated with estradiol (E) for 28 days supplemented with placebo or progesterone (P) on days 14-28 had reduced DNA fragmentation in serotonin neurons of the dorsal raphe nucleus, and long-term Ovx monkeys had fewer serotonin neurons than intact controls. We questioned the effect of E alone or E+P (estradiol supplemented with progesterone) on gene expression related to DNA repair, protein folding (chaperones), the ubiquitin-proteosome, axon transport and NDD-specific genes in serotonin neurons. Ovx macaques were treated with placebo, E or E+P (n=3 per group) for 1 month. Serotonin neurons were laser captured and subjected to microarray analysis and quantitative real-time PCR (qRT-PCR). Increases were confirmed with qRT-PCR in five genes that code for proteins involved in repair of strand breaks and nucleotide excision. NBN1, PCNA (proliferating nuclear antigen), GADD45A (DNA damage-inducible), RAD23A (DNA damage recognition) and GTF2H5 (gene transcription factor 2H5) significantly increased with E or E+P treatment (all analysis of variance (ANOVA), P

    Original languageEnglish (US)
    Pages (from-to)1565-1578
    Number of pages14
    JournalMolecular Psychiatry
    Volume20
    Issue number12
    DOIs
    StatePublished - Dec 1 2015

    Fingerprint

    Macaca
    DNA Repair
    Neurodegenerative Diseases
    Serotonin
    Steroids
    Gene Expression
    Neurons
    DNA Damage
    Haplorhini
    Progesterone
    Real-Time Polymerase Chain Reaction
    Estradiol
    Placebos
    Nuclear Antigens
    Protein Folding
    Amyotrophic Lateral Sclerosis
    Proliferating Cell Nuclear Antigen
    DNA Fragmentation
    Microarray Analysis
    Ubiquitin

    ASJC Scopus subject areas

    • Molecular Biology
    • Psychiatry and Mental health
    • Cellular and Molecular Neuroscience

    Cite this

    Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques. / Bethea, Cynthia; Reddy, Arubala.

    In: Molecular Psychiatry, Vol. 20, No. 12, 01.12.2015, p. 1565-1578.

    Research output: Contribution to journalArticle

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