Immunocytochemical localization of nuclear estrogen receptors and progestin receptors within the rat dorsal raphe nucleus

Alves, Stephen E.; Weiland, Nancy G.; Hayashi, Shigenari; McEwen, Bruce S.

doi:10.1002/(sici)1096-9861(19980216)391:3<322::aid-cne3>3.3.co;2-s

Cited by 12 publications

(10 citation statements)

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“…2H; 6A). Consistent with previous studies (Alves et al, 1998), additional dual label studies demonstrated that many of the ERβ-EGFP cells in the dorsal raphe contained 5-HT-ir (not shown). Scattered ERβ-EGFP cells were in the midline regions of the superior colliculus, the periaqueductal gray, intercollicular nucleus, pontine reticular nucleus (Fig.…”

Section: Resultssupporting

confidence: 89%

Distribution of estrogen receptor beta containing cells in the brains of bacterial artificial chromosome transgenic mice

et al. 2010

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In the brain, estrogen receptor β (ERβ) plays important roles in autonomic functions, stress reactivity and learning and memory processes. However, understanding the function of ERβ has been restricted by the limited availability of specific antisera, by difficulties discriminating the discrete localization of ERβ-immunoreactivity (ir) at the light microscopic level in many brain regions and the identification of ERβ-containing neurons in neurophysiological and molecular studies. Here, we demonstrate that a Esr2 bacterial artificial chromosome (BAC) transgenic mouse line that expresses ERβ identified by enhanced green fluorescent protein (EGFP) overcomes these shortcomings. Throughout the brain, ERβ-EGFP was detected in the nuclei and cytoplasm of cells, the majority of which resembled neurons. EGFP often extended into dendritic processes and could be identified either natively or following intensification of EGFP using immunolabeling. The distribution of ERβ-EGFP cells in brain closely corresponded to that reported for ERβ protein and mRNA. In particular, ERβ-EGFP cells were found in autonomic brain regions (i.e., hypothalamic paraventricular nucleus, rostral ventrolateral medulla and nucleus of the solitary tract), in regions associated with anxiety and stress behaviors (i.e., bed nucleus of the stria terminalis, amygdala, periaqueductal gray, raphe and parabrachial nuclei) and in regions involved in learning and memory processes (i.e., basal forebrain, cerebral cortex and hippocampus). Additionally, dual label light and electron microscopic studies in select brain areas demonstrate that cell containing ERβ-EGFP colocalize with both nuclear and extranuclear ERβ-immunoreactivity. These findings support the utility of Esr2 BAC transgenic reporter mice for future studies understanding the role of ERβ in CNS function.

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Section: Resultssupporting

confidence: 89%

Distribution of estrogen receptor beta containing cells in the brains of bacterial artificial chromosome transgenic mice

et al. 2010

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“…This antibody is a rabbit polyclonal against the native rat ERα and recognizes amino acids 61 through the carboxyl terminus. The specificity of this antibody has been previously demonstrated (Okamura et al, 1992; Alves et al, 1998; Milner et al, 2001). The antibody used for the detection of ERβ was a rabbit polyclonal from Merck Research Laboratories (Rahway, NJ) against a conserved sequence of amino acids 64–82 in the N-terminus which is not present in the ERα receptor (Mitra et al, 2003).…”

Section: Methodsmentioning

confidence: 80%

Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors

et al. 2009

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The hippocampal formation (HF) is involved in modulating learning related to drug abuse. While HF-dependent learning is regulated by both endogenous opioids and estrogen, the interaction between these two systems is not well understood. The mossy fiber (MF) pathway formed by dentate gyrus (DG) granule cell axons is involved in some aspects of learning and contains abundant amounts of the endogenous opioid peptide dynorphin (DYN). To examine the influence of ovarian steroids on DYN expression, we used quantitative light microscopic immunocytochemistry to measure DYN levels in normal cycling rats as well as in two established models of hormone-treated ovariectomized (OVX) rats. Rats in estrus had increased levels of DYN-immunoreactivity (ir) in the DG and certain CA3 lamina compared to rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 hrs showed increased DYN-ir in the DG and CA3, while those with 72 hrs estradiol exposure showed increases only in the DG. Six hrs of estradiol exposure produced no change in DYN-ir. OVX rats chronically implanted with medroxyprogesterone also showed increased DYN-ir in the DG and CA3. Next, dual-labeling electron microscopy (EM) was used to evaluate the subcellular relationships of estrogen receptor (ER) α-, ERβ and progestin receptor (PR) with DYN-labeled MFs. ERβ-ir was in some DYN -labeled MF terminals and smaller terminals, and had a subcellular association with the plasmalemma and small synaptic vesicles. In contrast, ERα-ir was not in DYN-labeled terminals, although some DYN-labeled small terminals synapsed on ERα-labeled dendritic spines. PR labeling was mostly in CA3 axons, some of which were continuous with DYN-labeled terminals. These studies indicate that ovarian hormones can modulate DYN in the MF pathway in a time-dependent manner, and suggest that hormonal effects on the DYN-containing MF pathway may be directly mediated by ERβ and/or PR activation.

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“…These studies demonstrated that ERα and ERβ have opposing effects on anxiety, in which ERα agonist, propyl-pyrazole-triol (PPT), is anxiogenic, whereas ERβ agonist, diarylpropionitrile (DPN), is anxioytic. The unique distributions of ERα and ERβ throughout the rat brain, including the subregions of the DRN (Shughrue et al, 1997, Alves et al, 1998, Lu et al, 2001), suggest a possible direct mechanism underlying the hormonal regulation of serotonergic neurons and may explain the bimodal effects on anxiety.…”

Section: Discussionmentioning

confidence: 99%

Estrogen decreases 5-HT1B autoreceptor mRNA in selective subregion of rat dorsal raphe nucleus: Inverse association between gene expression and anxiety behavior in the open field

Hiroi

Neumaier

2009

Neuroscience

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We have recently shown that estrogen decreases anxiety and increases expression of tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme for serotonin synthesis. However, the effects of estrogen on serotonin release and reuptake may also affect the overall availability of serotonin in the forebrain. Estrogen has been previously shown to have no effect on the inhibitory serotonin 1A autoreceptor (5-HT 1A ) in the rat dorsal raphe nuclei (DRN); however the regulation of the inhibitory serotonin 1B autoreceptor (5-HT 1B ) in the midbrain raphe by estrogen has not yet been investigated. Therefore, we examined the effects of estrogen on 5-HT 1B mRNA in the rat DRN, focusing on specific subregions, and whether 5-HT 1B mRNA levels correlated with TPH2 mRNA levels and with anxiety-like behavior. Ovariectomized rats were treated for two weeks with estrogen or placebo, exposed to the open field test, and 5-HT 1A and 5-HT 1B mRNA was quantified by in situ hybridization histochemistry. Estrogen had no effect on 5HT 1A mRNA in any of the DRN subregions examined, confirming a previous report. In contrast, estrogen selectively decreased 5-HT 1B mRNA in the midventromedial subregion of the DRN, where 5-HT 1B mRNA was associated with higher anxiety-like behavior and inversely correlated with TPH2 mRNA levels. These results suggest that estrogen may reduce 5-HT 1B autoreceptor and increase TPH2 synthesis in a coordinated fashion, thereby increasing the capacity for serotonin synthesis and release in distinct forebrain regions that modulate specific components of anxiety behavior. Keywordsserotonin; tryptophan hydroxylase; 5-HT 1A ; in situ hybridization; ovarian hormones; ovariectomy Women suffer from anxiety disorders at twice the rate of men (Palanza, 2001, Pigott, 2003, Steiner et al., 2003. Ovarian hormones, such as estrogen, are thought to play a significant role in regulation of anxiety, perhaps by modulating the serotonin (5-HT) system emanating from the dorsal raphe nucleus (DRN). The DRN, a major source of serotonergic innervation of the forebrain, plays a critical role in stress responsiveness (Maes and Meltzer, 1995, Sandford et al., 2000) and antidepressant drugs commonly used to treat anxiety disorders target the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 January 23. (Schneider et al., 1997, Zweifel and O'Brien, 1997, Zanardi et al., 2007.Animal studies show that estrogen alters the DRN 5-HT system at multiple control points, including synthesis, release and reuptake (...

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Immunocytochemical localization of nuclear estrogen receptors and progestin receptors within the rat dorsal raphe nucleus

Cited by 12 publications

References 53 publications

Distribution of estrogen receptor beta containing cells in the brains of bacterial artificial chromosome transgenic mice

Distribution of estrogen receptor beta containing cells in the brains of bacterial artificial chromosome transgenic mice

Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors

Estrogen decreases 5-HT1B autoreceptor mRNA in selective subregion of rat dorsal raphe nucleus: Inverse association between gene expression and anxiety behavior in the open field

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