Inhibitory Function of the Dorsomedial Hypothalamic Nucleus on the Hypothalamic-pituitary-adrenal Axis Response to an Emotional Stressor but Not Immune Challenge

Overview

Journal J Neuroendocrinol

Specialty Endocrinology

Date 2012 Aug 7

PMID 22861486

Citations 7

Authors

K Ebner

P Muigg

N Singewald

Affiliations

Soon will be listed here.

Abstract

Accumulating evidence implicates the dorsomedial hypothalamic nucleus (DMH) in the regulation of autonomic and neuroendocrine stress responses. However, although projections from the DMH to the paraventricular hypothalamic nucleus (PVN), which is the critical site of the neuroendocrine stress axis, have been described, the impact of DMH neurones in the modulation of hypothalamic-pituitary-adrenal (HPA) axis activation during stress is not fully understood. The present study aimed to investigate the role of the DMH in HPA axis responses to different types of stimuli. Male Sprague-Dawley rats fitted with a chronic jugular venous catheter were exposed to either an emotional stressor (elevated platform-exposure) or immune challenge (systemic interleukin-1β administration). Bilateral electrolytic lesions of the DMH disinhibited HPA axis responses to the emotional stressor, as indicated by higher plasma adrenocorticotrophic hormone levels during and after elevated platform exposure in lesioned animals compared to sham-lesioned controls. Moreover, DMH-lesioned animals showed increased neuronal activation in the PVN, as indicated by a higher c-Fos expression after elevated-platform exposure compared to controls. By contrast, DMH-lesions had no effects on HPA axis responses to immune challenge. Taken together, our data suggest an inhibitory role of DMH neurones on stress-induced HPA axis activation that is dependent upon the nature of the stimulus being important in response to an emotional stressor but not to immune challenge.

Citing Articles

PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus.

Ebner K, Fontebasso V, Ferro F, Singewald N, Hannibal J Neuropsychopharmacology. 2024; 50(3):519-530.

PMID: 39472527 PMC: 11735793. DOI: 10.1038/s41386-024-02016-9.

Olfactory modulation of stress-response neural circuits.

Shin M, Bae Y, Afzal R, Kondoh K, Lee E Exp Mol Med. 2023; 55(8):1659-1671.

PMID: 37524867 PMC: 10474124. DOI: 10.1038/s12276-023-01048-3.

The Central Inflammatory Network: A Hypothalamic fMRI Study of Experimental Endotoxemia in Humans.

Farber N, Manuel J, May M, Foadi N, Beissner F Neuroimmunomodulation. 2021; 29(3):231-247.

PMID: 34610606 PMC: 9254315. DOI: 10.1159/000519061.

Central insulin signaling modulates hypothalamus-pituitary-adrenal axis responsiveness.

Chong A, Vogt M, Hill A, Bruning J, Zeltser L Mol Metab. 2015; 4(2):83-92.

PMID: 25685696 PMC: 4314547. DOI: 10.1016/j.molmet.2014.12.001.

Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

Jarjisian S, Butler M, Paul M, Place N, Prendergast B, Kriegsfeld L J Biol Rhythms. 2014; 30(1):42-52.

PMID: 25512303 PMC: 4379209. DOI: 10.1177/0748730414561546.

References

Briski K, Gillen E . Differential distribution of Fos expression within the male rat preoptic area and hypothalamus in response to physical vs. psychological stress. Brain Res Bull. 2001; 55(3):401-8. DOI: 10.1016/s0361-9230(01)00532-9. View

Armario A . The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors?. CNS Neurol Disord Drug Targets. 2006; 5(5):485-501. DOI: 10.2174/187152706778559336. View

Kalsbeek A, Drijfhout W, Westerink B, van Heerikhuize J, van der Woude T, van der Vliet J . GABA receptors in the region of the dorsomedial hypothalamus of rats are implicated in the control of melatonin and corticosterone release. Neuroendocrinology. 1996; 63(1):69-78. DOI: 10.1159/000126937. View

Morin S, Dimicco J . Effect of microinjection of muscimol into the dorsomedial or paraventricular hypothalamic nucleus on air stress-induced neuroendocrine and cardiovascular changes in rats. Brain Res. 1996; 742(1-2):219-24. DOI: 10.1016/s0006-8993(96)01011-6. View

Bernardis L, Bellinger L . The dorsomedial hypothalamic nucleus revisited: 1998 update. Proc Soc Exp Biol Med. 1998; 218(4):284-306. DOI: 10.3181/00379727-218-44296. View

Silveira M, Zangrossi H, de Barros Viana M, Silveira R, Graeff F . Differential expression of Fos protein in the rat brain induced by performance of avoidance or escape in the elevated T-maze. Behav Brain Res. 2001; 126(1-2):13-21. DOI: 10.1016/s0166-4328(01)00233-9. View

Johnson P, Fitz S, Hollis J, Moratalla R, Lightman S, Shekhar A . Induction of c-Fos in 'panic/defence'-related brain circuits following brief hypercarbic gas exposure. J Psychopharmacol. 2010; 25(1):26-36. DOI: 10.1177/0269881109353464. View

Bellinger L, Bernardis L, MENDEL V . Effect of ventromedial and dorsomedial hypothalamic lesions on circadian corticosterone rhythms. Neuroendocrinology. 1976; 22(3):216-25. DOI: 10.1159/000122628. View

Arnold M, Langhans W . Effects of anesthesia and blood sampling techniques on plasma metabolites and corticosterone in the rat. Physiol Behav. 2010; 99(5):592-8. DOI: 10.1016/j.physbeh.2010.01.021. View

10.

Salchner P, Lubec G, Singewald N . Decreased social interaction in aged rats may not reflect changes in anxiety-related behaviour. Behav Brain Res. 2004; 151(1-2):1-8. DOI: 10.1016/j.bbr.2003.07.002. View

11.

Kiss A, Jezova D . Lesion of central part of the dorsomedial nucleus alters vasopressin but not corticotropin releasing hormone mRNA levels in rat hypothalamic paraventricular nucleus. Gen Physiol Biophys. 2002; 20(4):393-400. View

12.

Roland B, Sawchenko P . Local origins of some GABAergic projections to the paraventricular and supraoptic nuclei of the hypothalamus in the rat. J Comp Neurol. 1993; 332(1):123-43. DOI: 10.1002/cne.903320109. View

13.

Inglefield J, Schwarzkopf S, KELLOGG C . Alterations in behavioral responses to stressors following excitotoxin lesions of dorsomedial hypothalamic regions. Brain Res. 1994; 633(1-2):151-61. DOI: 10.1016/0006-8993(94)91534-2. View

14.

Vahl T, Ulrich-Lai Y, Ostrander M, Dolgas C, Elfers E, Seeley R . Comparative analysis of ACTH and corticosterone sampling methods in rats. Am J Physiol Endocrinol Metab. 2005; 289(5):E823-8. DOI: 10.1152/ajpendo.00122.2005. View

15.

Morin S, Dimicco J . Injection of muscimol in dorsomedial hypothalamus and stress-induced Fos expression in paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol. 2001; 280(5):R1276-84. DOI: 10.1152/ajpregu.2001.280.5.R1276. View

16.

DiMicco J, Samuels B, Zaretskaia M, Zaretsky D . The dorsomedial hypothalamus and the response to stress: part renaissance, part revolution. Pharmacol Biochem Behav. 2002; 71(3):469-80. DOI: 10.1016/s0091-3057(01)00689-x. View

17.

Herman J, Figueiredo H, Mueller N, Ulrich-Lai Y, Ostrander M, Choi D . Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol. 2003; 24(3):151-80. DOI: 10.1016/j.yfrne.2003.07.001. View

18.

Cullinan W, Herman J, Battaglia D, Akil H, Watson S . Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience. 1995; 64(2):477-505. DOI: 10.1016/0306-4522(94)00355-9. View

19.

Ulrich-Lai Y, Herman J . Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009; 10(6):397-409. PMC: 4240627. DOI: 10.1038/nrn2647. View

20.

Besedovsky H, Del Rey A, Klusman I, Furukawa H, Monge Arditi G, Kabiersch A . Cytokines as modulators of the hypothalamus-pituitary-adrenal axis. J Steroid Biochem Mol Biol. 1991; 40(4-6):613-8. DOI: 10.1016/0960-0760(91)90284-c. View