Location-specific Activation of the Paraventricular Nucleus of the Hypothalamus by Localized Inflammation

Overview

Journal Brain Behav Immun

Publisher Elsevier

Specialties Allergy & Immunology
Neurology
Psychiatry

Date 2010 Jun 24

PMID 20570615

Citations 16

Authors

Natalya Belevych

Krystal Buchanan

Qun Chen

Michael Bailey

Ning Quan

Affiliations

Soon will be listed here.

Abstract

The existence of an immunological homunculus has been proposed, but evidence for location-specific response of the central nervous system to immunological stimulation is lacking. In this study, we show that inflammation induced by injection of casein into one of the causes c-fos expression in the paraventricular nucleus of the hypothalamus (PVN) in an asymmetrical manner: much stronger activation is always induced in the contralateral PVN. Unilateral sciatic nerve transection abolished the casein-induced PVN activation if casein was injected into the hindlimb with the nerve transection, but had no effect if casein was injected into the hindlimb with intact nerve innervation. Injection of casein into one the forelimbs also caused contralateral PNV activation. Further, stronger PVN activation was found in the anterior PVN after the forelimb injection, but in the posterior PVN after the hindlimb injection. Casein-induced PVN activation is absent in IL-1R1 KO, IL-6 KO, TNFα KO, and in C3H/HeJ (TLR4 mutant) animals. In comparison, injection of LPS, a systemic inflammagen, into one hindlimb induced bilateral PVN activation but injection of live Escherichia coli into one hindlimb induced contralateral PVN activation. These results support the notion that local inflammation may activate the PVN by neural routes in a location-specific manner.

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References

Gaykema R, Chen C, Goehler L . Organization of immune-responsive medullary projections to the bed nucleus of the stria terminalis, central amygdala, and paraventricular nucleus of the hypothalamus: evidence for parallel viscerosensory pathways in the rat brain. Brain Res. 2006; 1130(1):130-45. DOI: 10.1016/j.brainres.2006.10.084. View

Brady L, Lynn A, Herkenham M, Gottesfeld Z . Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain. J Neurosci. 1994; 14(8):4951-64. PMC: 6577173. View

Brenn D, Richter F, Schaible H . Sensitization of unmyelinated sensory fibers of the joint nerve to mechanical stimuli by interleukin-6 in the rat: an inflammatory mechanism of joint pain. Arthritis Rheum. 2006; 56(1):351-9. DOI: 10.1002/art.22282. View

Oke S, Tracey K . From CNI-1493 to the immunological homunculus: physiology of the inflammatory reflex. J Leukoc Biol. 2007; 83(3):512-7. DOI: 10.1189/jlb.0607363. View

Turnbull A, Prehar S, Kennedy A, Little R, Hopkins S . Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice. Endocrinology. 2003; 144(5):1894-906. DOI: 10.1210/en.2002-220964. View

Ericsson A, Kovacs K, Sawchenko P . A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons. J Neurosci. 1994; 14(2):897-913. PMC: 6576823. View

Travers S, Travers J . Taste-evoked Fos expression in nitrergic neurons in the nucleus of the solitary tract and reticular formation of the rat. J Comp Neurol. 2006; 500(4):746-60. DOI: 10.1002/cne.21213. View

Akaishi T, Robbins A, Sakuma Y, Sato Y . Neural inputs from the uterus to the paraventricular magnocellular neurons in the rat. Neurosci Lett. 1988; 84(1):57-62. DOI: 10.1016/0304-3940(88)90337-0. View

Liu R, Qiang M, Qiao J . Nociceptive c-fos expression in supraspinal areas in avoidance of descending suppression at the spinal relay station. Neuroscience. 1998; 85(4):1073-87. DOI: 10.1016/s0306-4522(97)00662-3. View

10.

Goehler L, Gaykema R, Opitz N, Reddaway R, Badr N, Lyte M . Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun. 2005; 19(4):334-44. DOI: 10.1016/j.bbi.2004.09.002. View

11.

Imbe H, Dubner R, Ren K . Masseteric inflammation-induced Fos protein expression in the trigeminal interpolaris/caudalis transition zone: contribution of somatosensory-vagal-adrenal integration. Brain Res. 1999; 845(2):165-75. DOI: 10.1016/s0006-8993(99)01913-7. View

12.

Millan M . The induction of pain: an integrative review. Prog Neurobiol. 1999; 57(1):1-164. DOI: 10.1016/s0301-0082(98)00048-3. View

13.

Roth J, De Souza G . Fever induction pathways: evidence from responses to systemic or local cytokine formation. Braz J Med Biol Res. 2001; 34(3):301-14. DOI: 10.1590/s0100-879x2001000300003. View

14.

Cliffer K, Burstein R, Giesler Jr G . Distributions of spinothalamic, spinohypothalamic, and spinotelencephalic fibers revealed by anterograde transport of PHA-L in rats. J Neurosci. 1991; 11(3):852-68. PMC: 6575342. View

15.

Quan N, Banks W . Brain-immune communication pathways. Brain Behav Immun. 2007; 21(6):727-35. DOI: 10.1016/j.bbi.2007.05.005. View

16.

Gaykema R, Balachandran M, Godbout J, Johnson R, Goehler L . Enhanced neuronal activation in central autonomic network nuclei in aged mice following acute peripheral immune challenge. Auton Neurosci. 2006; 131(1-2):137-42. DOI: 10.1016/j.autneu.2006.07.005. View

17.

Bomholt S, Mikkelsen J, Blackburn-Munro G . Normal hypothalamo-pituitary-adrenal axis function in a rat model of peripheral neuropathic pain. Brain Res. 2005; 1044(2):216-26. DOI: 10.1016/j.brainres.2005.03.005. View

18.

Creasey A, Stevens P, Kenney J, Allison A, Warren K, Catlett R . Endotoxin and cytokine profile in plasma of baboons challenged with lethal and sublethal Escherichia coli. Circ Shock. 1991; 33(2):84-91. View

19.

Gaykema R, Daniels T, Shapiro N, Thacker G, Park S, Goehler L . Immune challenge and satiety-related activation of both distinct and overlapping neuronal populations in the brainstem indicate parallel pathways for viscerosensory signaling. Brain Res. 2009; 1294:61-79. PMC: 2748103. DOI: 10.1016/j.brainres.2009.07.076. View

20.

Roth J, Aslan T, Storr B, Zeisberger E . Lack of cross tolerance between LPS and muramyl dipeptide in induction of circulating TNF-alpha and IL-6 in guinea pigs. Am J Physiol. 1997; 273(4):R1529-33. DOI: 10.1152/ajpregu.1997.273.4.R1529. View