Effect of ovarian steroids on gene expression related to synapse assembly in serotonin neurons of macaques

Cynthia Bethea, Arubala Reddy

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Dendritic spines are the elementary structural units of neural plasticity. In a model of hormone replacement therapy (HT), we sought to determine the effect of estradiol (E) and progesterone (P) on gene expression related to synapse assembly in a laser-captured preparation enriched for serotonin neurons from rhesus macaques. Microarray analysis was conducted (n = 2 animals/treatment), and the results were confirmed for pivotal genes with qRT-PCR on additional laser-captured material (n = 3 animals/treatment). Ovariectomized rhesus macaques were treated with placebo, E, or E + P via Silastic implants for 1 month. The midbrain was obtained, sectioned, and immunostained for tryptophan hydroxylase (TPH). TPH-positive neurons were laser captured using an arcturus laser dissection microscope (Pixel II). RNA from laser-captured serotonin neurons was hybridized to Rhesus Affymetrix GeneChips for screening purposes. There was a twofold or greater change in the expression of 63 probe sets in the cell adhesion molecule (CAM) category, and 31 probe sets in the synapse assembly category were similarly altered in E- and E + P-treated animals. qRT-PCR assays showed that E treatment induced a significant increase in ephrin receptor A4 (EPHA4) and in integrin A8 (ITGA8) but not in ephrin receptor B4 (EPHB4) or integrin B8 (ITGB8) expression. E also increased expression of cadherin 11 (CDH11), neuroligin 3 (NLGN3), neurexin 3 (NRXN3), syndecan 2 (SCD2), and neural cell adhesion molecule (NCAM) compared with placebo. Supplemental P treatment suppressed E-induced gene expression. In summary, ovarian steroids target gene expression of adhesion molecules in serotonin neurons that are important for synapse assembly.

    Original languageEnglish (US)
    Pages (from-to)1324-1334
    Number of pages11
    JournalJournal of Neuroscience Research
    Volume90
    Issue number7
    DOIs
    StatePublished - Jul 2012

    Fingerprint

    Macaca
    Synapses
    Serotonin
    Lasers
    Steroids
    Gene Expression
    Neurons
    Tryptophan Hydroxylase
    Macaca mulatta
    Integrins
    EphA4 Receptor
    Syndecan-2
    Placebos
    Eph Family Receptors
    Neural Cell Adhesion Molecules
    Polymerase Chain Reaction
    Dendritic Spines
    Neuronal Plasticity
    Hormone Replacement Therapy
    Cell Adhesion Molecules

    Keywords

    • Affymetrix array
    • Cell adhesion molecules
    • Dorsal raphe
    • Estrogen
    • Macaques
    • Pro-gesterone
    • Quantitative PCR
    • Serotonin
    • Synapse assembly

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

    Cite this

    Effect of ovarian steroids on gene expression related to synapse assembly in serotonin neurons of macaques. / Bethea, Cynthia; Reddy, Arubala.

    In: Journal of Neuroscience Research, Vol. 90, No. 7, 07.2012, p. 1324-1334.

    Research output: Contribution to journalArticle

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    abstract = "Dendritic spines are the elementary structural units of neural plasticity. In a model of hormone replacement therapy (HT), we sought to determine the effect of estradiol (E) and progesterone (P) on gene expression related to synapse assembly in a laser-captured preparation enriched for serotonin neurons from rhesus macaques. Microarray analysis was conducted (n = 2 animals/treatment), and the results were confirmed for pivotal genes with qRT-PCR on additional laser-captured material (n = 3 animals/treatment). Ovariectomized rhesus macaques were treated with placebo, E, or E + P via Silastic implants for 1 month. The midbrain was obtained, sectioned, and immunostained for tryptophan hydroxylase (TPH). TPH-positive neurons were laser captured using an arcturus laser dissection microscope (Pixel II). RNA from laser-captured serotonin neurons was hybridized to Rhesus Affymetrix GeneChips for screening purposes. There was a twofold or greater change in the expression of 63 probe sets in the cell adhesion molecule (CAM) category, and 31 probe sets in the synapse assembly category were similarly altered in E- and E + P-treated animals. qRT-PCR assays showed that E treatment induced a significant increase in ephrin receptor A4 (EPHA4) and in integrin A8 (ITGA8) but not in ephrin receptor B4 (EPHB4) or integrin B8 (ITGB8) expression. E also increased expression of cadherin 11 (CDH11), neuroligin 3 (NLGN3), neurexin 3 (NRXN3), syndecan 2 (SCD2), and neural cell adhesion molecule (NCAM) compared with placebo. Supplemental P treatment suppressed E-induced gene expression. In summary, ovarian steroids target gene expression of adhesion molecules in serotonin neurons that are important for synapse assembly.",
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