Progesterone increased β-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration

Fernanda B. Lima, Cristiane M. Leite, Cynthia Bethea, Janete A. Anselmo-Franci

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    With the decline of ovarian steroids levels at menopause, many women experience an increase in anxiety and stress sensitivity. The locus coeruleus (LC), a central source of noradrenaline (NE), is activated by stress and is inhibited by β-endorphin. Moreover, increased NE has been implicated in pathological anxiety syndromes. Hormone replacement therapy (HRT) in menopause appears to decrease anxiety and vulnerability to stress. Therefore, we questioned the effect of HRT on the inhibitory β-endorphin innervation of the LC. In addition, we found that progesterone protects serotoninergic neurons in monkeys, leading us to question whether ovarian steroids are also neuroprotective in LC neurons in monkeys. Adult Rhesus monkeys (Macaca mulatta) were ovariectomized, and either treated with Silastic capsules that contained estradiol, estradiol + progesterone, progesterone alone or that were empty (ovariectomized; control). After 1 month, the LC was obtained and processed for immunohistochemistry for β-endorphin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The density of β-endorphin axons was determined with image analysis using ImageJ. The TUNEL-positive neurons were counted in the entire LC. Progesterone-alone significantly increased the density of the β-endorphin axons in the LC (p < 0.01). No significant differences between groups in the number of TUNEL-positive cells in the LC were found. In conclusion, we found that HRT increases the inhibitory influence of β-endorphin in the LC, which could, in turn, contribute to reduce anxiety and increase stress resilience. In addition, we did not find compelling evidence of neurodegeneration or neuroprotection by HRT in the LC of Rhesus monkeys.

    Original languageEnglish (US)
    Pages (from-to)1-8
    Number of pages8
    JournalBrain Research
    Volume1663
    DOIs
    StatePublished - May 15 2017

    Fingerprint

    Endorphins
    Locus Coeruleus
    Progesterone
    Steroids
    Hormone Replacement Therapy
    Anxiety
    Biotin
    Macaca mulatta
    Menopause
    Transferases
    Haplorhini
    Axons
    Estradiol
    Norepinephrine
    Serotonergic Neurons
    Neurons
    DNA Nucleotidylexotransferase
    Capsules
    Immunohistochemistry

    Keywords

    • Cell death
    • Locus coeruleus
    • Progesterone
    • Rhesus monkeys
    • Stress

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Developmental Biology
    • Clinical Neurology

    Cite this

    Progesterone increased β-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration. / Lima, Fernanda B.; Leite, Cristiane M.; Bethea, Cynthia; Anselmo-Franci, Janete A.

    In: Brain Research, Vol. 1663, 15.05.2017, p. 1-8.

    Research output: Contribution to journalArticle

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    abstract = "With the decline of ovarian steroids levels at menopause, many women experience an increase in anxiety and stress sensitivity. The locus coeruleus (LC), a central source of noradrenaline (NE), is activated by stress and is inhibited by β-endorphin. Moreover, increased NE has been implicated in pathological anxiety syndromes. Hormone replacement therapy (HRT) in menopause appears to decrease anxiety and vulnerability to stress. Therefore, we questioned the effect of HRT on the inhibitory β-endorphin innervation of the LC. In addition, we found that progesterone protects serotoninergic neurons in monkeys, leading us to question whether ovarian steroids are also neuroprotective in LC neurons in monkeys. Adult Rhesus monkeys (Macaca mulatta) were ovariectomized, and either treated with Silastic capsules that contained estradiol, estradiol + progesterone, progesterone alone or that were empty (ovariectomized; control). After 1 month, the LC was obtained and processed for immunohistochemistry for β-endorphin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The density of β-endorphin axons was determined with image analysis using ImageJ. The TUNEL-positive neurons were counted in the entire LC. Progesterone-alone significantly increased the density of the β-endorphin axons in the LC (p < 0.01). No significant differences between groups in the number of TUNEL-positive cells in the LC were found. In conclusion, we found that HRT increases the inhibitory influence of β-endorphin in the LC, which could, in turn, contribute to reduce anxiety and increase stress resilience. In addition, we did not find compelling evidence of neurodegeneration or neuroprotection by HRT in the LC of Rhesus monkeys.",
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