Behavioral phenotyping of mice deficient for tumor necrosis factor. D. V. Fursenko, N. V. Khotskin, V. A. Kulikov, A. V. Kulikov

Abstract:

The tumor necrosis factor (TNF) is a cytokine exerting both homeostatic and pathophysiological roles in the central nervous system (CNS). It has been demonstrated that TNF plays roles in such diseases as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Nevertheless, the role of TNF in the CNS under normal physiological conditions is poorly studied. A novel mouse strain with TNF deficiency (TNFKO) was developed in S.A. Nedospa­sov’s labora­tory of Engelhardt Institute of Molecular Bio­logy of the Russian Academy of Sciences on the C57Bl/6 (WT) background. In our study, we compared the behavior of TNFKO and WT adult mice in a battery of tests: open-field, elevated plus-maze and the forced-swim test. We showed that TNF deficiency had no effect on locomotor activity or exploration in the openfield test. At the same time, in this test, TNFKO mice spent more time in the center of the arena, but had a higher level of defecation and lower rearing duration. This result indicates that, in the openfield conditions, TNFKO mice show disorientation rather than anxiety-like behavior. There were no differences between TNFKO and WT in anxiety level in the elevated plus-maze test or in depressive-like behavior in the forcedswim test. These data suggest that TNF deficiency leads to changes in neurofunctional interactions that alter the mouse response to mild stress in the open-field test.

About The Authors:

D. V. Fursenko. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

N. V. Khotskin. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

V. A. Kulikov. Institute of Automation and Electrometry SB RAS, Russian Federation, Novosibirsk

A. V. Kulikov. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

References:

1. Belzung C., Griebel G. Measuring normal and pathological anxiety-like behavior in mice: a review. Behav. Brain Res. 2001;125:141-149.

2. Bradley J.R. TNF-mediated inflammatory disease. J. Pathol. 2008; 214(2):149-160. DOI:10.1002/path.2287

3. Camara M.L., Corrigan F., Jaehne E.J., Jawahar M.C., Anscomb H., Koerner H., Baune B.T. TNF-α and its receptors modulate complex behaviours and neurotrophins in transgenic mice. Psychoneuroendocrinology. 2013;38(12):3102-3114. DOI: 10.1016/j.psyneuen.2013.09.010

4. Crawley J.N. Behavioral phenotyping strategies for mutant mice. Neuron. 2008;57:809-818.

5. Cryan J.F., Mombereau C. In search of a depressive mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol. Psychiatry. 2004;9:326-357.

6. Dantzer R. Cytokine-induced sickness behavior: where do we stand? Brain Behav. Immun. 2001;15(1):7-24.

7. Denenberg V.H. Open-field behavior in the rat: What does it mean? Ann. N.Y. Acad. Sci. 1969;159:852-859.

8. Drutskaya M.S., Ortiz M., Liepinsh D.J., Kuprash D.V., Nedospasov S.A., Keller J.R. Inhibitory effects of tumor necrosis factor on hematopoiesis seen in vitro are translated to increased numbers of both committed and multipotent progenitors in TNF-deficient mice. Exp. Hematol. 2005;33(11):1348-1356.

9. Golan H., Levav T., Mendelsohn A., Huleihel M. Involvement of tumor necrosis factor alpha in hippocampal development and function. Cereb. Cortex. 2004;14(1):97-105.

10. Kaster M.P., Gadotti V.M., Calixto J.B., Santos A.R., Rodrigues A.L. Depressive-like behavior induced by tumor necrosis factor-α in mice. Neuropharmacology. 2012;62(1):419-426. DOI:10.1016/j.neuropharm.2011.08.018

11. Körner H., Cook M., Riminton D.S., Lemckert F.A., Hoek R.M., Ledermann B., Kontgen F., Fazekas de St. Groth B., Sedgwick J.D. Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue. Eur. J. Immunol. 1997;27(10):2600-2609.

12. Kulikov A.V., Morozova M.V., Kulikov V.A., Kirichuk V.S., Popova N.K. Automated analysis of antidepressants’ effect on the forced swim test. J. Neurosci. Meth. 2010;191:26-31.

13. Kulikov A.V., Tikhonova M.A., Kulikov V.A. Automated measurement of special preference in the open field test with transmitted lighting. J. Neurosci. Meth. 2008;170:345-351.

14. Kulikov A.V., Tikhonova M.A., Kulikova E.A., Volcho K.P., Khomenko T.M., Salakhutdinov N.F., Popova N.K. Antidepressant activity of 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153): Comparison with classical antidepressants. Lett. Drug Design Discov. 2014;11:169-173.

15. Kuprash D.V., Tumanov A.V., Liepinsh D.J., Koroleva E.P., Drutskaya M.S., Kruglov A.A., Shakhov A.N., Southon E., Murphy W.J., Tessarollo L., Grivennikov S.I., Nedospasov S.A. Novel tumor necrosis factor-knockout mice that lack Peyer’s patches. Eur. J. Immunol. 2005;35(5):1592-1600.

16. Li J., Ramenaden E.R., Peng J., Koito H., Volpe J.J., Rosenberg P.A. Tumor necrosis factor alpha mediates lipopolysaccharide-induced microglial toxicity to developing oligodendrocytes when astrocytes are present. J. Neurosci. 2008;28(20):5321-5330. DOI: 10.1523/JNEUROSCI.3995-07.2008

17. Marino M.W., Dunn A., Grail D., Inglese M., Noguchi Y., Richards E., Jungbluth A., Wada H., Moore M., Williamson B., Basu S., Old L.J. Characterization of tumor necrosis factor-deficient mice. Proc. Natl Acad. Sci. USA. 1997;94(15):8093-8098.

18. McAfoose J., Koerner H., Baune B.T. The effects of TNF deficiency on age-related cognitive performance. Psychoneuroendocrinology. 2009;34(4):615-619. DOI: 10.1016/j.psyneuen.2008.10.006

19. McCoy M.K., Tansey M.G. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J. Neuroinflammation. 2008;5(45). DOI: 10.1186/1742-2094-5-45

20. Milner L.C., Crabbe J.C. Three murine anxiety models: results from multiple inbred strain comparison. Genes Brain Behav. 2008;7:496-505.

21. Montgomery S.L., Bowers W.J. Tumor necrosis factor-alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system. J. Neuroimmune Pharmacol. 2012;7(1): 42-59. DOI: 10.1007/s11481-011-9287-2

22. Pasparakis M., Alexopoulou L., Episkopou V., Kollias G. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J. Exp. Med. 1996;184(4):1397-1411.

23. Pellow S., Chopin P., File S.E., Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Meth. 1985;14:149-167.

24. Porsolt R.D., Le Pichon M., Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977;266:730-732.

25. Prut L., Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur. J. Pharmacol. 2003;463:3-33.

26. Schioppa T., Moore R., Thompson R.G., Rosser E.C., Kulbe H., Nedospasov S., Mauri C., Coussens L.M., Balkwill F.R. B regulatory cells and the tumor-promoting actions of TNF-? during squamous carcinogenesis. Proc. Natl Acad. Sci. USA. 2011;108(26):10662-10667. DOI: 10.1073/pnas.1100994108

27. Standford C. The open field test: reinventing the weel. J. Psychopharmacol. 2007;21:134-135.

28. Tecott L.H. The genes and brain of mice and men. Am. J. Psychiatry. 2003;160:646-656.

29. Wahlsten D., Rustay N.R., Metten P., Crabbe J.C. In search of a better mouse test. Trends Neurosci. 2003;26:132-136.

30. Willner P. Animal models of depression: an overview. Pharmacol. Ther. 1990;45:425-455.

31. Willner P., Mitchell P.J. The validity of animal models of predisposition to depression. Behav. Pharmacol. 2002;13:169-188.

32. Yamada K., Iida R., Miyamoto Y., Saito K., Sekikawa K., Seishima M., Nabeshima T. Neurobehavioral alterations in mice with a targeted deletion of the tumor necrosis factor-alpha gene: implications for emotional behavior. J. Neuroimmunol. 2000;111(1/2):131-8.

This entry was posted in Tom 19-4. Bookmark the permalink.