Cited by 289Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior

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A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry

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Chan, RK, Brown, ER, Ericsson, A, Kovacs, KJ, Sawchenko, PE·1993·The Journal of Neuroscience

DOI 10.1523/jneurosci.13-12-05126.1993PMC PMC6576398

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Abstract

The promoter regions of the rat corticotropin-releasing factor (CRF), oxytocin (OT), and vasopressin (AVP) genes contain sequences similar to the cis-acting response element identified for NGFI-B, an immediate- early gene structurally related to the steroid hormone receptor superfamily. Combined immuno- and hybridization histochemical approaches were used to determine whether challenges that influence the synthesis and secretion of CRF, OT, and/or AVP result in altered expression in neurosecretory neurons of NGFI-B and another immediate- early gene, c-fos, which is widely used as a marker for functionally activated neurons. NGFI-B mRNA was found to be expressed at constitutively high levels in the telencephalon, but not in the endocrine hypothalamus, of unperturbed controls; basal levels of c-fos expression were uniformly low throughout the CNS. NGFI-B and c-fos mRNAs, and Fos protein, were induced with a similar time course and in similar neuroendocrine cell types in response to acute hypotensive hemorrhage (15% reduction in blood volume), intravenous injection of interleukin-1 beta (IL-1 beta; 1.87 micrograms/kg), chronic salt loading (7 d maintenance on 2% saline), and acute bilateral adrenalectomy. c-fos mRNA and Fos protein were readily demonstrable in afferent pathways that have been implicated as mediating the neuroendocrine responses in the three stress paradigms; these include medullary catecholaminergic cell groups in response to IL-1 beta and hemorrhage, and cell groups lining the lamina terminalis in response to salt loading. Challenge-specific induction of NGFI-B expression was detectable in these extrahypothalamic cell groups, though with a lesser sensitivity than that required to reveal NGFI-B induction in the hypothalamus, or c-fos expression in these related afferents. These results establish NGFI-B as a useful adjunct to c-fos, for revealing synaptic and/or transcriptional activation in the magno- and parvocellular neurosecretory systems. Differences in the sensitivity of the two markers in revealing functionally related activation in extrahypothalamic regions speak to general issues concerning the use of immediate-early genes in mapping functional circuitry in the CNS.

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Authors: Chan, R., Brown, E., Ericsson, A., Kovacs, K., & Sawchenko, P.
Affiliations: Salk Institute for Biological Studies (US)
ORCID: Ericsson, A
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1993-12-01
Volume: 13
Issue: 12
Pages: 5126-5138
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.13-12-05126.1993
PMC: PMC6576398
OpenAlex: W1824948378
Cited by: 289
References: 56
Citations by year: 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 8 · 2013: 5 · 2012: 3
FWCI: 8.79
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Xerox Foundation
International Research and Exchanges Board
Fondation pour la Recherche Médicale
National Institutes of Health (5r01hl035137-15)
Medical Research Council
National Heart, Lung, and Blood Institute (HL-35137)
Fogarty International Center
National Institute of Neurological Disorders and Stroke (NS21182)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Keywords: Nur77, c-fos, immediate early genes, corticotropin-releasing factor, oxytocin, vasopressin, stress response, Fos protein, hemorrhage, IL-1β, salt loading, adrenalectomy, lamina terminalis, catecholaminergic neurons, hypothalamus, telencephalon, gene expression biomarkers
MeSH terms: Adrenalectomy, Animals, Arginine Vasopressin, Base Sequence, Corticotropin-Releasing Hormone, DNA-Binding Proteins, Hemorrhage, Male, Molecular Sequence Data, Neurosecretory Systems, Oxytocin, Paraventricular Hypothalamic Nucleus, Receptors, Steroid, RNA, Messenger, Sodium Chloride, Stress, Physiological, Transcription Factors, Gene Expression, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Rats, Nuclear Receptor Subfamily 4, Group A, Member 1

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A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry

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