Corticotropin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study.

ABSTRACT The discovery of a 41-amino acid peptide with potent corticotropin-releasing factor properties has prompted a search for neurons that contain this substance and potentially utilize it in intercellular communication. The present study utilized immunohistochemical methods and an antiserum directed against a synthetic replica of ovine corticotropin-releasing factor. The rat hypothalamus was found to contain striking immunoreactive groups of neuronal perikarya within the paraventricular, periventricular, and anterior hypothalamic nuclei, some of which are likely to project to the external layer of the median eminence and thereby comprise a hypophysiotropic system. Certain other hypothalamic nuclei, as well as many other regions of the central nervous system, were found to contain corticotropin-releasing factor-immunoreactive neurons. Among the most prominent of these were neurons in the bed nucleus of stria terminalis, the central nucleus of the amygdala, the region of the dorsal raphe, locus ceruleus, the external cuneate nucleus, and the medullary reticular formation. Thus, corticotropin-releasing factor, like many other neurohormones and peptides, may participate in neuroendocrine regulation as well as play a role as a neurotransmitter-like substance in numerous extrahypothalamic circuits.

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    ABSTRACT: Corticotrophin-releasing factor (CRF) plays a key role in initiating many of the endocrine, autonomic, and behavioral responses to stress. CRF-containing neurons of the paraventricular nucleus of the hypothalamus (PVN) are classically involved in regulating endocrine function through activation of the stress axis. However, CRF is also thought to play a critical role in mediating anxiety-like responses to environmental stressors, and dysfunction of the CRF system in extra-hypothalamic brain regions, like the bed nucleus of stria terminalis (BNST), has been linked to the etiology of many psychiatric disorders including anxiety and depression. Thus, although CRF neurons of the PVN and BNST share a common neuropeptide phenotype, they may represent two functionally diverse neuronal populations. Here, we employed dual-immunofluorescence, single-cell RT-PCR, and electrophysiological techniques to further examine this question and report that CRF neurons of the PVN and BNST are fundamentally different such that PVN CRF neurons are glutamatergic, whereas BNST CRF neurons are GABAergic. Moreover, these two neuronal populations can be further distinguished based on their electrophysiological properties, their co-expression of peptide neurotransmitters such as oxytocin and arginine-vasopressin, and their cognate receptors. Our results suggest that CRF neurons in the PVN and the BNST would not only differ in their response to local neurotransmitter release, but also in their action on downstream target structures.
    Frontiers in Neuroscience 01/2013; 7:156. DOI:10.3389/fnins.2013.00156
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed drugs in psychiatry. Based on the fact that SSRIs increase extracellular monoamine levels in the brain, the monoamine hypothesis of depression was introduced, postulating that depression is associated with too low serotonin, dopamine and noradrenaline levels. However, several lines of evidence indicate that this hypothesis is too simplistic and that depression and the efficacy of SSRIs are dependent on neuroplastic changes mediated by changes in gene expression. Because a coherent view on global gene expression is lacking, we aim to provide an overview of the effects of SSRI treatment on the final targets of 5-HT receptor signal transduction pathways, namely the transcriptional regulation of genes. We address gene polymorphisms in humans that affect SSRI efficacy, as well as in vitro studies employing human-derived cells. We also discuss the molecular targets affected by SSRIs in animal models, both in vivo and in vitro. We conclude that serotonin transporter gene variation in humans affects the efficacy and side-effects of SSRIs, whereas SSRIs generally do not affect serotonin transporter gene expression in animals. Instead, SSRIs alter mRNA levels of genes encoding serotonin receptors, components of non-serotonergic neurotransmitter systems, neurotrophic factors, hypothalamic hormones and inflammatory factors. So far little is known about the epigenetic and age-dependent molecular effects of SSRIs, which might give more insights in the working mechanism(s) of SSRIs.
    Pharmacology [?] Therapeutics 08/2012; 136(3). DOI:10.1016/j.pharmthera.2012.08.015 · 7.75 Impact Factor
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    ABSTRACT: Mice and rats are widely used in stress-related behavioral studies while little is known about the distribution of the stress hormone, corticotropin-releasing factor (CRF) in the mouse brain. We developed and characterized a novel rat/mouse CRF polyclonal antibody (CURE ab 200101) that was used to detect and compare the brain distributions of CRF immunoreactivity in naïve and colchicine-treated rats and mice. We also assessed whether the visceral stressor of abdominal surgery activated brain CRF neurons using double labeling of Fos/CRF in naïve rats. CRF-ir neurons were visualized in the cortex, bed nucleus of the stria terminalis, central amygdala, hypothalamic paraventricular nucleus (PVN), Barrington's nucleus and dorsolateral tegmental area in naïve rats. CRF-immunoreactive (ir) neurons in the mouse brain were detected only after colchicine. The pattern shows fundamental similarity compared to the colchicine-treated rat brain, however, there were differences with a lesser distribution in both areas and density except in the lateral septum and external subnucleus of the lateral parabrachial nucleus which contained more CRF-ir neurons in mice, and CRF-ir neurons in the dorsal motor nucleus of the vagus were found only in mice. Abdominal surgery in naïve rats induced Fos-ir in 30% of total CRF-ir neurons in the PVN compared with control (anesthesia alone) while Fos was not co-localized with CRF in other brain nuclei. These data indicate that CRF-ir distribution in the brain displays similarity as well as distinct features in mice compared to rats that may underlie some differential stress responses. Abdominal surgery activates CRF-ir neurons selectively in the PVN of rats without colchicine treatment.
    Brain research 07/2011; 1415:34-46. DOI:10.1016/j.brainres.2011.07.024 · 2.83 Impact Factor


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