Skip to main content

Long-term disorders of behavior in rats induced by administration of tumor necrosis factor during early postnatal ontogenesis

Neuroscience and Behavioral Physiology volume 39, pages 21–24 (2009)Cite this article

The proinflammatory cytokine tumor necrosis factor α (TNFα) is one of the main mediators of neuroimmune interactions. Increased production of TNFα in nerve and immune system cells occurs in infectious diseases, traumas, ischemia, and hypoxia. The present study addressed the role of TNFα in the formation of behavior during early postnatal ontogenesis. TNFα was given to rats during the third week of life and behavior was tested at ages 1.5 and 3 months using the open field test and the elevated plus maze test. Experimental rats differed from controls in terms of changes in orientational behavior on testing at 1.5 months and an increase in anxiety on testing at 1.5 and 3 months. The different roles of proinflammatory cytokines in the brain at the early stages of ontogenesis are discussed.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. O. E. Zubareva, A. P. Eliseeva, A. S. Simbirtseva, and V. M. Klimenko, “Effects of proinflammatory cytokines on the formation of behavior in early postnatal ontogenesis,” Ros. Fiziol. Zh. im. I. M. Sechenova, 91, No. 4, 374–384 (2005).

    CAS  Google Scholar 

  2. O. E. Zubareva, O. M. Efremov, A. S. Simbirtsev, and V. M. Klimenko, “Interleukin-1 and depressive states,” Ros. Fiziol. Zh. im. I. M. Sechenova, 87, No. 10, 1450–1456 (2001).

    CAS  Google Scholar 

  3. V. M. Klimenko and O. E. Zubareva, “The neurobiology of cytokines, behavior, and adaptive reactions,” Ros. Fiziol. Zh. im. I. M. Sechenova, 85, No. 9–10, 1244–1254 (1999).

    CAS  Google Scholar 

  4. H. Aly, M. T. Khashaba, M. El-Ayouty, O. El-Sayed, and B. M. Hasanein, “IL-lbeta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy,” Brain Dev., 28, No. 3, 178–182 (2006).

    PubMed  Article  Google Scholar 

  5. A. I. Bartha, A. Foster-Barber, S. P. Miller, D. B. Vigneron, D. V. Glidden, A. J. Berkerovich, and D. M. Ferriero, “Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome,” Pediatr. Res., 56, No. 6, 960–966 (2004).

    PubMed  Article  CAS  Google Scholar 

  6. R. M. Bluthe, M. Pawlowski, S. Suarez, P. Parnet, Q. Pittman, K. W. Kelley, and R. Dantzer, “Synergy between tumor necrosis factor alpha and interleukin-1 in the induction of sickness behavior in mice,” Psychoneuroendocrinology, 19, No. 2, 197–207 (2004).

    Article  Google Scholar 

  7. E. S. Bont, A. Martens, J. van Raan, G. Samson, W. P. Getter, A. Okken, and L. H. de Leif, “Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma levels in neonatal sepsis,” Pediatr. Res., 33, No. 4, Part 1, 380–383 (1993).

    PubMed  Article  Google Scholar 

  8. K. Brebner, S. Hayley, R. Zacharko, Z. Merali, and H. Anisma, “Synergistic effects of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha: central monoamine, corticosterone, and behavioral variations,” Neuropsychopharmacology, 22, No. 6, 566–580 (2000).

    PubMed  Article  CAS  Google Scholar 

  9. Z. Cai, S. Lin, Y. Pang, and P. G. Rhodes, “Brain injury induced by intracerebral injection of interleukin-1 beta and tumor necrosis factor-alpha in the neonatal rat,” Pediatr. Res., 56, No. 3, 377–384 (2004).

    PubMed  Article  CAS  Google Scholar 

  10. W. Cammer, “Apoptosis of oligodendrocytes in secondary cultures from neonatal rat brains,” Neurosci. Lett., 327, No. 2, 123–127 (2002).

    PubMed  Article  CAS  Google Scholar 

  11. T. J. Connor, C. L. Song, B. E. Leonard, Z. Merali, and H. Anisman, “An assessment of the effects of central interleukin-1 beta,-2,-6, and tumor necrosis factor-alpha administration on some behavioural, neurochemical, endocrine and immune parameters in the rat,” Neurosci., 84, No. 3, 923–933 (1998).

    Article  CAS  Google Scholar 

  12. J. Croonenberghs, E. Bosmans, D. Deboutte, G. Kenis, and M. Maes, “Activation of the inflammatory response system in autism,” Neuropsychobiology, 45, No. 1, 1–6 (2002).

    PubMed  Article  CAS  Google Scholar 

  13. M. Fiore, E. Alleva, L. Probert, G. Kollias, F. Angelucci, and L. Aloe, “Exploratory and displacement behavior in transgenic mice expressing high levels of brain TNF-alpha,” Physiol. Behav., 63, No. 4, 571–576 (1998).

    PubMed  Article  CAS  Google Scholar 

  14. S. Kurimiya, Y. Miura, K. Nakatsuji, M. Dodo, M. Ori, and T. Ito, “General pharmacology of recombinant human tumor necrosis factor. 2nd communication: effects on central nervous system functions,” Arzneimittelforschung, 40, No. 2, Part 1, 225–231 (1990).

    Google Scholar 

  15. T. Mizuno, M. Sawada, A. Suzumura, and T. Marunouchi, “Expression of cytokines during glial differentiation,” Brain Res., 656, No. 1, 141–146 (1994).

    PubMed  Article  CAS  Google Scholar 

  16. D. M. Orentas and R. H. Miller, “Regulation of oligodendrocyte development,” Mol. Neurobiol., 18, No. 3, 247–259 (1998).

    PubMed  Article  CAS  Google Scholar 

  17. N. Oygüt, O. Sünmez, O. Saka, and O. Yegin, “Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-α and interleukin-1β concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy,” Arch. Dis. Child. Fetal Neonatol., 79, No. 3, F190–F193 (1998).

    Article  Google Scholar 

  18. A. Ozdemir, N. Oygur, M. Gultekind, M. Coskun, and O. Yegin, “Neonatal tumor necrosis factor, interleukin-1 alpha, interleukin-l beta, and interleukin-6 response to infection,” Ann. J. Perinatol., 11, No. 4, 282–285 (1994).

    Article  CAS  Google Scholar 

  19. R. C. Silveira and R. S. Procianoy, “Interleukin-6_and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy,” J. Pediatr., 143, No. 5, 625–629 (2003).

    PubMed  Article  CAS  Google Scholar 

  20. Y. Sun, J. W. Calvert, and J. H. Zhang, “Neonatal hypoxia/ischemia is associated with decrease inflammatory mediator after erythropoietin administration,” Stroke, 36, No. 8, 1672–1678 (2005).

    PubMed  Article  CAS  Google Scholar 

  21. H. D. Venters, R. Dantzer, and K. W. Kelley, “A new concept in neurodegeneration: TNF-alpha is a silencer of survival signals,” Trends Neurosci., 23, No. 4, 175–190 (2000).

    PubMed  Article  CAS  Google Scholar 

  22. K. Yamasu, H. Onoe, G. Soma, H. Oshima, and D. Mizuno, “Secretion of tumor necrosis factor during fetal and neonatal development of the mouse: ontogenic inflammation,” J. Biol. Response Mod., 8, No. 6, 644–655 (1989).

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. State Research Institute of Experimental Medicine, Russian Academy of Medical Sciences, 12 Academician Pavlov Street, 197376, St. Petersburg, Russia

    O. E. Zubareva & V. M. Klimenko

Authors
  1. O. E. Zubareva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. M. Klimenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 1, pp. 14–19, January, 2008.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zubareva, O.E., Klimenko, V.M. Long-term disorders of behavior in rats induced by administration of tumor necrosis factor during early postnatal ontogenesis. Neurosci Behav Physi 39, 21–24 (2009). https://doi.org/10.1007/s11055-008-9090-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-008-9090-6

Key Words

  • tumor necrosis factor α
  • early postnatal ontogenesis
  • anxiety
  • investigative behavior