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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
Open accessAbstract
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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“we employed Fos, a widely used marker, to map neuronal activation throughout the brain after the two types of stress.16,17,19,45”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [17]
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Metadata
- 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
- 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
- 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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