Background and Aim: Toxoplasma gondii is an intracellular parasite that commonly infects warm-blooded animals, including humans. Virtually all species can be infected, but a species-specific variability is evident, in terms of both type and severity of the symptoms encountered. As serotonin (5-hydroxytryptamine [5-HT]) plays an important regulatory role in both physiological and immune responses, the aim of this research was to assess whether toxoplasmosis disease could affect plasma 5-HT concentration and/or hematochemical parameters in a particularly susceptible species to infection as sheep.

Materials and Methods: 5-HT plasma levels were analyzed in platelet-poor plasma fraction by enzyme-linked immunosorbent assay. Blood count and hematochemical parameters were evaluated. Total proteins (TPs), glucose (Glu), and lactate dehydrogenase were determined by a spectrophotometer.

Results: Results showed significantly higher levels in plasma 5-HT, monocytes, and TP and significantly lower levels of Glu, in infected sheep compared to the control group.

Conclusion: Results could support the hypothesis of an effect of toxoplasmosis infection on plasma 5-HT concentrations in sheep. More research is needed to assess the function of 5-HT in the regulation of infected sheep's immune responses.

Keywords: monocytes, plasma, serotonin, serum, sheep, toxoplasmosis.

1. Center for Disease Control and Prevention (CDC), United States. (2017) Available from: http://www.cdc.gov/ncidod/dpd/parasites/toxoplasmosis/default.htm. Last accessed on 13-03-2018.

2. Webster, J.P., Kaushik, M., Bristow, G.C. and McConkey, G.A. (2013) Toxoplasma gondii infection, from predation to schizophrenia: Can animal behavior help us understand human behaviour? J. Exp. Biol., 216(1): 99-112. [Crossref] [PubMed] [PMC]

3. Hsu, P.C., Groer, M. and Beckie, T. (2014) New findings: Depression, suicide, and Toxoplasma gondii infection. J. Am. Assoc. Nurse Pract., 26(11): 629-637. [Crossref] [PubMed]

4. Pearce, B.D., Kruszon-Moran, D. and Jones, J.L. (2012) The relationship between Toxoplasma gondii infection and mood disorders in the third national health and nutrition survey. Biol. Psychiatry, 72(4): 290-295. [Crossref] [PubMed] [PMC]

5. Gatkowska, J., Wieczorek, M., Dziadek, B., Dzitko, K. and Dlugonska, H. (2013) Sex-dependent neurotransmitter level changes in brains of Toxoplasma gondii infected mice. Exp. Parasitol., 133(1): 1-7. [Crossref] [PubMed]

6. Bertrand, P.P. and Bertrand, R.L. (2010) Serotonin release and uptake in the gastrointestinal tract. Auton. Neurosci., 153(1-2): 47-57. [Crossref] [PubMed]

7. Brenner, B., Harney, J.T., Ahmed, B.A., Jeffus, B.C., Unal, R., Mehta, J.F. and Kilic, F. (2007) Plasma serotonin levels and the platelet serotonin transporter. J. Neurochem., 102(1): 206-215. [Crossref] [PubMed] [PMC]

8. Ito, T., Ikeda, U., Shimpo, M., Yamamoto, K. and Shimada, K. (2000) Serotonin increases interleukin-6 synthesis in human vascular smooth muscle cells. Circulation, 102(20): 2522-2527. [Crossref] [PubMed]

9. Nau, F. Jr, Yu, B., Martin, D. and Nichols, C.D. (2013) Serotonin 5-HT2A receptor activation blocks TNF-a mediated inflammation in vivo. PLoS One, 8(10): e75426. [Crossref] [PubMed] [PMC]

10. Cloez-Tayarani, I., Petit-Bertron, A.F., Venters, H.D. and Cavaillon, J.M. (2003) Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: Involvement of 5-hydroxytryptamine2A receptors. Int. Immunol., 15(2): 233-240. [Crossref] [PubMed]

11. Fiebich, B.L., Akundi, R.S., Lieb, K., Candelario-Jalil, E., Gmeiner, D., Haus, U., Muller, W., Stratz, T. and Mu-oz, E. (2004) Antiinflammatory effects of 5-HT3 receptor antagonists in lipopolysaccharide-stimulated primary human monocytes. Scand. J. Rheumatol. Suppl., 33(s119): 28-32. [Crossref]

12. Tsuchida, Y., Hatao, F., Fujisawa, M., Murata, T., Kaminishi, M., Seto, Y., Hori, M. and Ozaki, H. (2011) Neuronal stimulation with 5-hydroxytryptamine 4 receptor induces anti-inflammatory actions via a7nACh receptors on muscularis macrophages associated with postoperative ileus. Gut, 60(5): 638-647. [Crossref] [PubMed] [PMC]

13. Herr, N., Bode, C. and Duerschmied, D. (2017) The effects of serotonin in immune cells. Front Cardiovasc. Med., 4: 48. [Crossref] [PubMed] [PMC]

14. Xiao, J., Li, Y., Prandovszky, E., Karuppagounder, S.S., Talbot Junior, C.C., Dawson, V.L., Dawson, T.M. and Yolken, R.H. (2014) MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway. Neuroscience, 268: 128-138. [Crossref] [PubMed] [PMC]

15. Goodwin, D., Hrubec, T.C., Klein, B.G., Strobl, J.S., Were, S.R., Han, Q., Zajac, A.M. and Lindsay, D.S. (2012) Congenital infection of mice with Toxoplasma gondii induces minimal change in behavior and no change in neurotransmitter concentrations. J. Parasitol., 98(4): 706-712. [Crossref] [PubMed]

16. Opsteegh, M., Shares, G., Blaga, R. and van der Giessen, J. On Behalf of the Consortium (2016) Experimental Studies of Toxoplasma gondii in the Main Livestock Species, (GP/EFSA/BIOHAZ/2013/01). Final Report, EFSA Supporting Publication, EN-995, 161. [Crossref]

17. Drewry, L.L. and Sibley, L.D. (2017) Toxoplasma gondii infection reprograms monocyte adherence and motility. Faseb J., 31(Suppl.1): 776.9.

18. Blume, M., Rodriguez-Contreras, D., Landfear, S., Fleige, T., Soldati-Favre, D., Lucius, R. and Gupta, N. (2009) Host-derived glucose and its transporter in the obligate intracellular pathogen Toxoplasma gondii are dispensable by glutaminolysis. Proc. Natl. Acad. Sci. U S A, 106(31): 12998-13003. [Crossref] [PubMed] [PMC]

19. Nitzsche, R., Zagoriy, V., Lucius, R. and Gupta, N. (2016) Metabolic cooperation of glucose and glutamine is essential for the lytic cycle of obligate intracellular parasite Toxoplasma gondii. J. Biol. Chem., 291(1): 126-141. [Crossref] [PubMed] [PMC]

20. Agha, F., Sadaruddin, A. and Ghafoor, A. (1992) Immunoglobulins and serum proteins in toxoplasmosis. J. Pak. Med. Assoc., 42(2): 42-43. [PubMed]

21. Portas, T.J. (2010) Toxoplasmosis in macropodids: A review. J. Zoo Wildl. Med., 41(1): 1-6. [Crossref] [PubMed]

22. McAllister, M.M. (2005) A decade of discoveries in veterinary protozoology changes our concept of "subclinical" toxoplasmosis. Vet. Parasitol., 132(3-4): 241-247. [Crossref] [PubMed]

23. Arzt, E., Costas, M., Finkielman, S. and Nahmod, V.E. (1991) Serotonin inhibition of tumor necrosis factor-alpha synthesis by human monocytes. Life Sci., 48(26): 2557-2562. [Crossref]

24. Kubera, M., Maes, M., Kenis, G., Kim, Y.K. and Lason, W. (2005) Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor alpha and interleukin-6. Psychiatry Res., 134(3): 251-258. [Crossref] [PubMed]

25. Mossner, R. and Lesch, K.P. (1998) Role of serotonin in the immune system and in neuroimmune interactions. Brain Behav. Immun., 12(4): 249-271. [Crossref] [PubMed]

26. McMorran, B.J., Marshall, V.M., de Graaf, C., Drysdale, K.E., Shabbar, M., Smyth, G.K., Corbin, J.E., Alexander, W.S. and Foote, S.J. (2009) Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science, 323(5915): 797-800. [Crossref] [PubMed]

---