Glucocorticoid receptor-immunoreactivity in corticotrophin-releasing factor afferents to the locus coeruleus

The stress-related neurohormone, corticotropin-releasing factor (CRF), also acts as a neurotransmitter to activate the brain noradrenergic nucleus, locus coeruleus (LC). Previous electrophysiological findings demonstrating that tonic CRF secretion in the LC is increased in adrenalectomized rats sugg...

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Bibliographic Details
Published in:Brain research 1999-01, Vol.816 (1), p.17-28
Main Authors: Lechner, Sandra M, Valentino, Rita J
Format: Article
Language:English
Subjects:
Amygdala - metabolism
Anatomy
Animals
Axonal Transport
Barrington's nucleus
Bed nucleus of the stria terminalis
Biological and medical sciences
Central nervous system
Central nucleus of the amygdala
Corticotropin-releasing factor
Corticotropin-Releasing Hormone - metabolism
Fundamental and applied biological sciences. Psychology
Glucocorticoid receptor
Immunohistochemistry
Locus coeruleus
Locus Coeruleus - metabolism
Male
Neurons, Afferent - metabolism
Norepinephrine
Paraventricular Hypothalamic Nucleus - metabolism
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid - metabolism
Vertebrates: nervous system and sense organs
Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate - metabolism
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Summary:The stress-related neurohormone, corticotropin-releasing factor (CRF), also acts as a neurotransmitter to activate the brain noradrenergic nucleus, locus coeruleus (LC). Previous electrophysiological findings demonstrating that tonic CRF secretion in the LC is increased in adrenalectomized rats suggest that activity of certain CRF afferents to the LC is under inhibitory regulation by endogenous corticosteroids. The present study was designed to identify putative CRF afferents to the LC that may be regulated by glucocorticoids. Retrograde tract tracing from the rat LC and pericoerulear regions was combined with immunohistochemistry to visualize CRF and glucocorticoid receptors in the same sections of rat brain. The retrograde tracer, wheat germ agglutinin conjugated to horseradish peroxidase coupled to gold (WGA–Au–HRP) was injected into either the nucleus LC or the rostrolateral pericoerulear region (peri-LC), where CRF-immunoreactive terminals have been demonstrated to synapse with LC dendrites. Sections were processed to visualize the tracer, as well as CRF- and glucocorticoid receptor-immunoreactivity. Following injections of WGA–Au–HRP into the nuclear LC, triple labeled neurons were observed primarily in Barrington's nucleus, where 74±4% of retrogradely labeled CRF-immunoreactive neurons colocalized glucocorticoid receptor immunoreactivity. In contrast, injections that incorporated the rostrolateral peri-LC retrogradely labeled numerous neurons that were immunoreactive for both CRF and glucocorticoid receptors in the central nucleus of the amygdala. Thus, 94±2% of the retrogradely labeled CRF-immunoreactive neurons in the central nucleus of the amygdala colocalized glucocorticoid receptor immunoreactivity. Additionally, triple labeled neurons were observed in the bed nucleus of the stria terminalis following WGA–Au–HRP injections that incorporated the rostrolateral peri-LC. The present results implicate Barrington's nucleus, the central nucleus of the amygdala and the bed nucleus of the stria terminalis as glucocorticoid-sensitive sources of CRF that can influence the LC-noradrenergic system. Alterations in glucocorticoid levels or glucocorticoid receptor function would be predicted to affect the impact of these specific CRF systems on LC activity.
ISSN:0006-8993
1872-6240
DOI:10.1016/S0006-8993(98)00900-7