Skip to main content
Log in

Comparative Analysis of the Responses of Orexin-Containing Neurons to Administration of Different Doses of Lipopolysaccharide

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Many studies are currently addressing the involvement of orexin-containing hypothalamic neurons in the responses of the CNS to administration of antigens, particularly lipopolysaccharide (LPS). The dynamics of changes in the number of orexin-containing neurons in hypothalamic structures in brain slices were assessed 2, 4, and 6 h after administration of LPS at a low, non-septic dose. Comparative analysis of the responses of orexin-containing neurons after administration of a non-septic and a higher, subseptic, dose of LPS was performed. LPS at a dose of 25 μg/kg was followed 2 and 4 h later by increases in the numbers of orexin-positive neurons, with subsequent decreases in numbers, while the higher LPS dose of 500 μg/kg altered the neuron count only at 6 h, with a more significant decline in the number of orexin-containing neurons. These data provide evidence for changes in the content of orexin detected within neurons and a change in the balance of orexin synthesis and utilization processes in response to administration of an antigen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yu. V. Gavrilov, S. V. Perekrest, and N. S. Novikova, “Expression of c-Fos protein in cells in various structures of the hypothalamus in electrical pain stimulation and administration of antigens,” Ros. Fiziol. Zh. im. I. M. Sechenova, 92, No. 10, 1195–1203 (2006).

    CAS  Google Scholar 

  2. E. A. Korneva and L. M. Khai, “Effects of lesioning of parts of the hypothalamic area on the process of immunogenesis,” Fiziol. Zh. SSSR, 49, No. 1, 42–48 (1963).

    CAS  PubMed  Google Scholar 

  3. V. A. Lesnikov, “Neurohumoral mechanisms of regulation of the functions of the red bone marrow as a source of hematopoietic stem cells,” in: Immunophysiology [in Russian], E. A. Korneva (ed.), Nauka, St. Petersburg (1993), pp. 294–315.

    Google Scholar 

  4. S. V. Perekrest,Yu. V. Gavrilov, T. V. Abramova, N. S. Novikova, and E. A. Korneva, “Activation of cells in hypothalamic structures on administration of different types of antigen (in terms of c-fos gene expression),” Med. Immunol., 8, No. 5–6, 631–636 (2006).

    Google Scholar 

  5. S. Baatout, “Interleukin-6 and megakaryocytopoiesis: an update,” Ann. Hematol., 73, 157–162 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. C. Becskei, H. Riediger, D. Hernadfalvy, A. Arsenijevic, T. A. Lutz, and W. Langhans, “Inhibitory effects of lipopolysaccharide on hypothalamic nuclei implicated in the control of food intake,” Brain Behav. Immunol., 22, No. 1, 56–64 (2008).

    Article  CAS  Google Scholar 

  7. C. T. Beckmann and M. Yanagisawa, “Orexin: from neuropeptides to energy homeostasis and sleep/wake regulation,” J. Mol. Med., 80, 329–342 (2004).

    Article  Google Scholar 

  8. M. G. Dube, S. P. Kalra, and P. S. Kalra, “Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action,” Brain Res., 842, 473–477 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. J. K. Elmquist and C. B. Saper, “Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide,” J. Comp. Neurol., 374, No. 3, 315–331 (1996).

    Article  CAS  PubMed  Google Scholar 

  10. R. A. Espana, B. A. Baldo, A. E. Kelley, and C. W. Berridge, “Wakepromoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action,” Neurosci., 106, No. 4, 699–715 (2001).

    Article  CAS  Google Scholar 

  11. R. P. Gaykema, S. M. Park, C. R. McKibbin, and L. E. Goehler, “Lipopolysaccharide suppresses activation of the tuberomammillary histaminergic system concomitant with behavior: a novel target of immune-sensory pathways,” Neurosci., 152, No. 1, 273–287 (2008).

    Article  CAS  Google Scholar 

  12. R. P. A. Gaykema, L. E. Goehler, C. B. Armstrong, J. Khorsand, S. F. Maier, and L. R. Watkins, “Differential FOS expression rat brain induced by lipopolysaccharide and staphylococcal enterotoxin B,” Neuroimmunomodul., 6, 220 (1999).

    Google Scholar 

  13. L. E. Goehler, R. P. A. Gaykema, and K. Hansen, “Staphylococcal enterotoxin B induces fever, brain c-Fos expression, and scrum corticosterone in rats,” Am. J. Regul. Integ. Comp. Physiol., 280, R1434–R1439 (2001).

    Google Scholar 

  14. G. J. Hervieu, J. E. Cludery, D. C. Harrison, J. C. Roberts, and R. A. Leslie, “Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord,” Neurosci., 103, 777–797 (2001).

    Article  CAS  Google Scholar 

  15. T. Ida, K. Nakahara, T. Katayama, N. Murakami, and M. Kakazato, “Effect of lateral cerebro-ventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats,” Brain Res., 821, 526–529 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. T. Ida, K. Nakahara, T. Murakami, R. Hanada, M. Nakazato, and N. Murakami, “Possible involvement of orexin in the stress reaction in rats,” Biochem. Biophys. Res. Commun., 270, 318–323 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. M. Kopf, L. LeGros, A. J. Coyle, M. Kosco-Vilbois, and F. Brombacher, “Immune responses of IL-4, IL-5, IL-6 deficient mice,” Immunol. Rev., 148, 45–69 (1995).

    Article  CAS  PubMed  Google Scholar 

  18. S. Lacroix and D. Rivest, “Functional circuitry in the brain of immune-challenged rats: Partial involvement of prostaglandins,” J. Comp. Neurol., 387, 307–324 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. X. C. Ma, J. Oliver, E. Horvath, and C. P. Phelps, “Cytokine and adrenal axis responses to endotoxin,” Brain Res., 861, 135–142 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. G. D. Martich, R. L. Fanner, M. Coska, and A. E. Suffredini, “Detection of interleukin-8 and tumor necrosis factor in normal humans after intravenous endotoxin: The effects of anti-inflammatory agents,” J. Exp. Med., 173, 1021–1024 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. S.-M. Park, R. P. A. Gaykema, and L. E. Goehler, “How does immune challenge inhibit ingestion of palatable food? Evidence that systemic lipopolysaccharide treatment modulates key nodal points of feeding neurocircuitry,” Brain Behav. Immun., 22, No. 8, 1160–1172 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. S. V. Perekrest, T. V. Abramova, N. S. Novikova, Yu. V. Loskutov, V. J. Rogers, and E. A. Korneva, “Changes in immunoreactivity of orexin-A-positive neurons after an intravenous lipopolysaccharide injection,” Med. Sci. Monit., 14, No. 7, BR127–BR133 (2008).

    Google Scholar 

  23. C. Peyron, D. K. Tighe,A. N. van den Pol, L. de Lecea, H. C. Heller, G. Sutcliffe, and Th. S. Kilduff, “Neurons containing hypocretin (orexin) project to multiple neuronal systems,” J. Neurosci., 18, No. 23, 9996–10015 (1998).

    CAS  PubMed  Google Scholar 

  24. C. Phelps and L.-T. Chen, “Brain response to endotoxin,” in: Cytokines and the Brain, C. Phelps and E. Korneva (eds.), Elsevier (2008), pp. 435–455.

  25. H. S. Randeva, E. Karteris, D. Grammatopoulos, and E. W. Hillhouse, “Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis,” J. Clin. Endocrinol. Metab., 86, No. 10, 4808–4813 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. N. J. Rothwell and S. J. Hopkins, “Cytokines and the nervous system: II. Actions and mechanisms of action,” Trends Neurosci., 18, 130–136 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. S. N. Shanin, E. G. Rybakina, N. S. Novikova, I. A. Kozinets, V. J. Rogers, and E. A. Korneva, “Natural killer cell cytotoxic activity and c-Fos protein synthesis in rat hypothalamic cells after painful electric stimulation of the hind limbs and EHF irradiation of the skin,” Med. Sci. Monit., 11, No. 9, BR309–BR315 (2005).

    Google Scholar 

  28. U. Steidl, S. Bork, S. Schaub, O. Selbach, J. Seres, M. Aivado, Th. Schroeder, U.-P. Rohr, R. Fenk, S. Kliszewski, Ch. Maercker, P. Neubert, S. R. Bornstein, H. L. Haas, G. Kobbe, D. G. Tenen, R. Haas, and R. Kronenwett, “Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators,” Blood, 104, 81–88 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. L. W. Swanson, G. Sanchez-Watts, and A. G. Watts, “Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone,” Neurosci. Lett., 387, 80–84 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. L. W. Swanson, Brain Maps. III. Structure of the Rat Brain, Elsevier Academic Press, San Diego (2004), 3rd Ed.

    Google Scholar 

  31. S. Taheri, M. Mahmoodi, J. Opacka-Juffiry, M. A. Ghatei, and S. R. Bloom, “Distribution and quantification of immunoreactive orexin A in rat tissues,” FEBS Lett., 457, 157–161 (1999).

    Article  CAS  PubMed  Google Scholar 

  32. S. Taheri, D. Sunter, C. Dakin, S. Moyes, L. Seal, J. Gardiner, M. Rossi, M. Ghatei, and S. R. Bloom, “Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system,” Neurosci. Lett., 279, No. 1/2, 109–112 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. P. Trivedi, H. Yu, D. J. MacNeil, L. H. van der Ploeg, and X. M. Guan, “Distribution of orexin receptor mRNA in the rat brain,” FEBS Lett., 438, 71–75 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. S. Watanabe, T. Kuwaki, M. Yanagisawa, Y. Fukuda, and M. Shimoyama, “Persistent pain and stress activate pain-inhibitory orexin pathways,” Neuroreport, 16, No. 1, 5–8 (2005).

    Article  PubMed  Google Scholar 

  35. M. Wenner, N. Kawamura, and T. Ishikawa, “Reward linked to increased natural killer cell activity in rats,” Neuroimmunomod., 7, 1–5 (2000).

    Article  CAS  Google Scholar 

  36. Yi-Hong, J. K. Jan Lu, J. K. Elmquist, and C. B. Saper, “Lipopolysaccharide activates specific populations of hypothalamic and brainstem neurons that project of the spinal cord,” J. Neurosci., 20, No. 17, 6578–6586 (2000).

    Google Scholar 

  37. S. Zhang, D. Blache, P. E. Vercoe, C. L. Adam, M. A. Blackberry, P. A. Findlay, K. A. Eidne, and G. B. Martin, “Expression of orexin receptors in the brain and peripheral tissues of the male sheep,” Regul. Pept., 124, 81–87 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. V. Perekrest.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 95, No. 12, pp. 1336–1345, December, 2009.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perekrest, S.V., Abramova, T.V. & Novikova, N.S. Comparative Analysis of the Responses of Orexin-Containing Neurons to Administration of Different Doses of Lipopolysaccharide. Neurosci Behav Physi 41, 206–212 (2011). https://doi.org/10.1007/s11055-011-9401-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-011-9401-1

Key words

Navigation