Advertisement

LPS-Induced c-Fos Activation in NTS Neurons and Plasmatic Cortisol Increases in Septic Rats Are Suppressed by Bilateral Carotid Chemodenervation

  • Edison-Pablo Reyes
  • Sebastián Abarzúa
  • Aldo Martin
  • Jorge Rodríguez
  • Paula P. Cortés
  • Ricardo FernándezEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)

Abstract

Lipopolysaccharide (LPS) administered i.p. increases significantly the activation of c-Fos in neurons of the nucleus of the solitary tract (NTS), which in turn activates hypothalamus-pituitary-adrenal axis. The vagus nerve appears to play a role in conveying cytokines signals to the central nervous system (CNS), since -in rodent models of sepsis- bilateral vagotomy abolishes increases in plasmatic glucocorticoid levels, but does not suppress c-Fos NTS activation. Considering that NTS also receives sensory inputs from carotid body chemoreceptors, we evaluated c-Fos activation and plasmatic cortisol levels 90 min after i.p. administration of 15 mg/kg LPS. Experiments were performed in male Sprague–Dawley rats, in control conditions and after bilateral carotid neurotomy (BCN). LPS administration significantly increases the number of c-Fos positive NTS neurons and plasmatic cortisol levels in animals with intact carotid/sinus nerves. When LPS was injected after BCN, the number of c-Fos positive NTS neurons, and plasmatic cortisol levels were not significantly modified. Our data suggest that carotid body chemoreceptors might mediate CNS activation during sepsis.

Keywords

LPS Inflammation Carotid sinus nerve c-Fos NTS 

Notes

Acknowledgments

Special thanks are due to Mrs. Carolina Larraín for proofreading the manuscript. This work was supported by grant DI-40-11/R (to RF), from the Division for Research of the Universidad Andres Bello (UNAB).

References

  1. Berthoud HR, Kressel M, Neuhuber WL (1995) Vagal afferent innervation of rat abdominal paraganglia as revealed by anterograde DiI-tracing and confocal microscopy. Acta Anat (Basel) 152:127–132CrossRefGoogle Scholar
  2. Bluthe RM, Walter V, Parnet P, Laye S, Lestage J, Verrier D, Poole S, Stenning BE, Kelley KW, Dantzer R (1994) Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad Sci III 317:499–503PubMedGoogle Scholar
  3. Dantzer R, Konsman JP, Bluthe RM, Kelley KW (2000) Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci 85:60–65PubMedCrossRefGoogle Scholar
  4. De Laurentis A, Pisera D, Caruso C, Candolfi M, Mohn C, Rettori V, Seilicovich A (2002) Lipopolysaccharide- and tumor necrosis factor–induced changes in prolactin secretion and dopaminergic activity in the hypothalamic-pituitary axis. Neuroimmunomodulation 10:30–39CrossRefGoogle Scholar
  5. Del Río R, Moya EA, Iturriaga R (2011) Differential expression of pro-inflammatory cytokines, endothelin-1 and nitric oxide synthases in the rat carotid body exposed to intermittent hypoxia. Brain Res 1395:74–85PubMedCrossRefGoogle Scholar
  6. Emch GS, Hermann GE, Rogers RC (2000) TNF-alpha activates solitary nucleus neurons responsive to gastric distension. Am J Physiol Gastrointest Liver Physiol 279:G582–G586PubMedGoogle Scholar
  7. Fernandez R, Gonzalez S, Rey S, Cortes PP, Maisey KR, Reyes EP, Larrain C, Zapata P (2008) Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha. Exp Physiol 93:892–907PubMedCrossRefGoogle Scholar
  8. Fernandez R, Nardocci G, Simon F, Martin A, Becerra A, Rodriguez-Tirado C, Maisey KR, Cuna-Castillo C, Cortes PP (2011) Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome. Respir Physiol Neurobiol 175:336–348PubMedCrossRefGoogle Scholar
  9. Hermann GE, Rogers RC (2009) TNF activates astrocytes and catecholaminergic neurons in the solitary nucleus: implications for autonomic control. Brain Res 1273:72–82PubMedCrossRefGoogle Scholar
  10. Hermann GE, Emch GS, Tovar CA, Rogers RC (2001) c-Fos generation in the dorsal vagal complex after systemic endotoxin is not dependent on the vagus nerve. Am J Physiol Regul Integr Comp Physiol 280:R289–R299PubMedGoogle Scholar
  11. Hoffman GE, Smith MS, Verbalis JG (1993) c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. Front Neuroendocrinol 14:173–213PubMedCrossRefGoogle Scholar
  12. Hosoi T, Okuma Y, Matsuda T, Nomura Y (2005) Novel pathway for LPS-induced afferent vagus nerve activation: possible role of nodose ganglion. Auton Neurosci 120:104–107PubMedCrossRefGoogle Scholar
  13. Lam SY, Tipoe GL, Liong EC, Fung ML (2008) Chronic hypoxia upregulates the expression and function of proinflammatory cytokines in the rat carotid body. Histochem Cell Biol 130:549–559PubMedCrossRefGoogle Scholar
  14. Liu X, He L, Stensaas L, Dinger B, Fidone S (2009) Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. Am J Physiol Lung Cell Mol Physiol 296:L158–L166PubMedCrossRefGoogle Scholar
  15. Mac Grory B, O’Connor ET, O’Halloran KD, Jones JF (2010) The effect of pro-inflammatory cytokines on the discharge rate of vagal nerve paraganglia in the rat. Respir Physiol Neurobiol 171:122–127PubMedCrossRefGoogle Scholar
  16. Mascorro JA, Yates RD (1980) Paraneurons and paraganglia: histological and ultrastructural comparisons between intraganglionic paraneurons and extra-adrenal paraganglion cells. Adv Biochem Psychopharmacol 25:201–213PubMedGoogle Scholar
  17. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ (2003) The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 9:125–134PubMedGoogle Scholar
  18. Paxinos G, Watson CR (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, Burlington, p 456Google Scholar
  19. Steinman L (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5:575–581PubMedCrossRefGoogle Scholar
  20. Wan W, Wetmore L, Sorensen CM, Greenberg AH, Nance DM (1994) Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. Brain Res Bull 34:7–14PubMedCrossRefGoogle Scholar
  21. Zapata P, Larrain C, Reyes P, Fernandez R (2011) Immunosensory signalling by carotid body chemoreceptors. Respir Physiol Neurobiol 178:370–374PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Edison-Pablo Reyes
    • 1
  • Sebastián Abarzúa
    • 2
  • Aldo Martin
    • 2
  • Jorge Rodríguez
    • 3
  • Paula P. Cortés
    • 2
  • Ricardo Fernández
    • 4
    Email author
  1. 1.Facultad de MedicinaClínica Alemana-Universidad del DesarrolloSantiagoChile
  2. 2.Departamento de Ciencias Biologicas, Facultad de Ciencias BiologicasUniversidad Andres BelloSantiagoChile
  3. 3.Facultad de Medicina, Escuela de MedicinaUniversidad Andres BelloSantiagoChile
  4. 4.Departamento de Ciencias Biologicas, Facultad de Ciencias BiologicasUniversidad Andres BelloSantiagoChile

Personalised recommendations