Serotonin-related gene expression in female monkeys with individual sensitivity to stress

Bethea, Cynthia L.; Streicher, John M.; Mirkes, Stephanie J.; Sanchez, Rachel L.; Reddy, Arubala P.; Cameron, Judy L.

doi:10.1016/j.neuroscience.2004.11.022

Cited by 67 publications

(83 citation statements)

References 78 publications

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“…That is, macaques with higher endogenous production of E and P and higher expression of genes related to serotonin neurotransmission, maintained ovulatory function upon exposure to a combined stress paradigm of diet, exercise and new housing (Bethea et al, 2005b). The current study demonstrates that the same 1-month HT paradigm that increases serotonin function also decreases CRH expression in the PVN at gene and protein levels.…”

Section: Discussionmentioning

confidence: 50%

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Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Bethea

Centeno

2007

Neuropsychopharmacol

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Corticotropin-releasing hormone (CRH) gene and protein expression were examined in the paraventricular nucleus (PVN) of ovariectomized female macaques treated with placebo or hormone therapy (HT) consisting of either estrogen (E) for 28 days, or progesterone (P) for the last 14 of 28 days, or E for 28 days supplemented with P for the last 14 of 28 days using Silastic capsules implanted s.c. in the periscapular region (n ¼ 4/group). Perfusion fixed sections (25 mm) at five levels of the PVN (rostral to caudal at 250 mm intervals) were immunostained (ICC) with an antibody to human CRH or processed in an in situ hybridization (ISH) assay with a monkey specific CRH riboprobe. The immunostained CRH-positive area was quantified with a Marianas Stereology Workstation and Slidebook 4.2. There was a significant decrease in the immunological CRH signal with E, P, and E + P treatment as measured by total or average pixels and microns (analysis of variance (ANOVA), po0.002; Student-Newman-Keul's post hoc test versus placebo control group, po0.05). There was also a decrease in the number of detectable CRH neurons (ANOVA, po0.03) with HT. The sections processed for ISH were exposed to autoradiographic films. The CRH mRNA signal was analyzed with NIH Image. The average optical density and positive pixel area of the CRH mRNA signal was significantly suppressed by ovarian HT (ANOVA po0.002; StudentNewman-Keul's post hoc test versus placebo control group, po0.05). In summary, 1 month of stable treatment with a moderate dose of E, P or E + P significantly reduced CRH mRNA and protein in the PVN of ovariectomized monkeys. These results suggest that this hormone treatment regimen may increase stress resilience in surgically menopausal primates.

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Section: Discussionmentioning

confidence: 50%

“…Before these analyses, measurements of estradiol, and P on this platform were compared to traditional RIAs as reported previously (Bethea et al, 2005b).…”

Section: Hormone Assaysmentioning

confidence: 99%

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Bethea

Centeno

2007

Neuropsychopharmacol

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“…38 In stress-sensitive female monkeys, SERT mRNA was found to be decreased specifically in the caudal subnucleus. 39 Although 5-HT levels were not measured in these studies, both of these findings are consistent with a compensatory response to deficient serotonergic neurotransmission.…”

Section: Discussionmentioning

confidence: 51%

Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

et al. 2008

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Deficient levels of serotonin are associated with suicide and depression. Paradoxically, in the dorsal raphe nucleus (DRN) there are more serotonin neurons and more neuronal tryptophan hydroxylase-2 (TPH2) expression postmortem in depressed suicides. In this study, we sought to determine whether greater TPH2 expression in depressed suicides was the result of more TPH2 expression per neuron. In situ hybridization and computer-assisted image analysis were performed on tissue sections throughout the extent of the raphe nuclei at the level of silver grains per neuron to systematically quantify TPH2 neuronal expression. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls (P = 0.04). The difference in grain density is greater at mid-and caudal anatomical levels across the rostrocaudal axis of the DRN. Densitometric analysis of TPH2 expression in the DRN subnuclei showed that higher expression levels were observed at posterior anatomical levels of depressed suicides (121% of control in the caudal subnucleus). Higher TPH2 expression in depressed suicides may explain more TPH2 protein and reflect a homeostatic response to deficient serotonin levels in the brains of depressed suicides. Localized changes in TPH2 expression in specific subnuclei of the DRN suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus.

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“…SS monkeys have suppressed physiological release of serotonin (6), fewer serotonergic cells, and low expression of a number of genes in the serotonin pathway, including FEV1, TPH2, SERT, MAO-A, and MAO-B, in the dorsal raphe nucleus (5,7). Moreover, treatment with a selective serotonin reuptake inhibitor, citalopram, increases ovarian steroid hormone secretion in SS monkeys (14).…”

Section: Discussionmentioning

confidence: 99%

Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis

Herod

Dettmer²,

Novak

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Serotonin-related gene expression in female monkeys with individual sensitivity to stress

Cited by 67 publications

References 78 publications

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis

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