Long-term ovariectomy decreases serotonin neuron number and gene expression in free ranging macaques

Cynthia Bethea, A. W. Smith, M. L. Centeno, Arubala Reddy

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    The serotonin system responds to the ovarian steroids, estradiol (E) and progesterone (P), in women and female animal models. In macaques, ovarian steroid administration to ovariectomized (Ovx) individuals improves serotonin neural function through actions on pivotal serotonin-related genes and proteins, such as TPH2 (tryptophan hydroxylase 2), SERT (serotonin reuptake transporter), and the 5HT1A autoreceptor. In addition, ovarian steroid administration reduces gene and protein expression in the caspase-independent pathway and reduces DNA fragmentation in serotonin neurons. This study examines the hypothesis that long-term ovariectomy will lead to a loss of serotonin neurons and compromised gene expression in serotonin neurons. Female Japanese macaques were ovariectomized or tubal ligated (n=5/group) at 3 years of age and returned to their natal troop. After 3 years, the animals were collected, administered a fenfluramine challenge to determine global serotonin availability, and then euthanized. Fev, TPH2, SERT, and 5HT1A expression were examined with digoxigenin in situ hybridization (ISH) and quantitative image analysis. Cell number, positive pixel area, and average pixel density were determined. In the Ovx group, Fev, TPH2, SERT, and 5HT1A showed a significant decease in average and total cell number and positive pixel area. The reduction in Fev-positive neurons suggests that there were fewer serotonin neurons in Ovx animals compared to ovary-intact animals. The decrease in TPH2 in the Ovx animals was consistent with earlier results in 5-month Ovx animals, but it may be due to the decrease in cell number rather than a decrease in expression on an individual cell basis. The decrease in SERT and 5HT1A in long-term Ovx differed from previous studies in short-term Ovx. In summary, long-term ovarian steroid loss resulted in fewer serotonin neurons and overall lower Fev, TPH2, SERT, and 5HT1A gene expression. This may be due to serotonin cell death or to a negative impact on a long-term developmental process in young female macaques.

    Original languageEnglish (US)
    Pages (from-to)675-688
    Number of pages14
    JournalNeuroscience
    Volume192
    DOIs
    StatePublished - Sep 29 2011

    Fingerprint

    Macaca
    Ovariectomy
    Serotonin
    Tryptophan Hydroxylase
    Gene Expression
    Neurons
    Serotonin Plasma Membrane Transport Proteins
    Steroids
    Cell Count
    Fenfluramine
    Digoxigenin
    Autoreceptors
    DNA Fragmentation
    Caspases
    In Situ Hybridization
    Progesterone
    Ovary
    Estradiol
    Proteins
    Cell Death

    Keywords

    • 5HT1A autoreceptor
    • Estrogen
    • Fenfluramine
    • Fev
    • Progesterone
    • Serotonin reuptake transporter
    • TPH2

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Long-term ovariectomy decreases serotonin neuron number and gene expression in free ranging macaques. / Bethea, Cynthia; Smith, A. W.; Centeno, M. L.; Reddy, Arubala.

    In: Neuroscience, Vol. 192, 29.09.2011, p. 675-688.

    Research output: Contribution to journalArticle

    Bethea, Cynthia ; Smith, A. W. ; Centeno, M. L. ; Reddy, Arubala. / Long-term ovariectomy decreases serotonin neuron number and gene expression in free ranging macaques. In: Neuroscience. 2011 ; Vol. 192. pp. 675-688.
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