, 2012). In Chagas disease, a neglected tropical disease caused by the protozoan parasite

Trypanosoma cruzi ( Lannes-Vieira et al., 2010), evidence of central nervous system (CNS) abnormalities in chronic patients includes alterations in quantitative electroencephalograms, sleep dysfunction, memory impairment and depression ( Prost et al., 2000 and Silva et al., 2010), although the causes of these manifestations remain elusive. In the acute phase of infection, T. cruzi colonizes the CNS of humans and experimental models ( Pittella, 2009 and Silva et al., 2010). The transition from acute to chronic infection is accompanied by a decline in systemic parasite load and CNS parasitism in response to an effective immune response ( Roffê et al., 2003, Junqueira et al., 2010 and Silva et al., 2010). In contrast to the cardiomyopathy associated with myocarditis ( Histone Demethylase inhibitor Freitas et al., 2005), inflammation in the CNS is rare in the chronic phase, even though

the parasite persists in the nervous tissue in an apparently silent manner ( Silva et al., 2010). The existence of a chronic nervous form of Chagas disease remains a matter of debate ( Silva et al., 2010). Although neurologic involvement has been considered to be independent of heart lesions ( Prost et al., 2000), neurocognitive dysfunctions and mood disorders such as depression have been proposed as secondary consequences of inflammatory heart disease ( Mosovich et al., 2008). The severity of

Chagas’ heart disease is associated with an immune dysbalance that favors IFNγ and TNF over interleukin (IL)-10 in the cardiac tissue and periphery ( Dutra et al., Doramapimod in vivo 2009). However, the participation of cytokines in mood disorders associated with Chagas disease has not been explored. In an attempt to understand the complexity of the involvement of the CNS in T. cruzi infection, we have previously shown that C3H/He (H-2k) mice infected with the Colombian strain develop severe meningoencephalitis with enrichment in macrophages and CD8+ T-cells that is restricted to the acute infection, whereas C57BL/6 (H-2b) mice are resistant to T. cruzi-induced meningoencephalitis ( Silva et al., 1999 and Roffê selleck chemicals et al., 2003). In both mouse lineages, acute myocarditis progresses to chronic cardiomyopathy that occurs in a pro-inflammatory milieu ( Medeiros et al., 2009 and Silverio et al., 2012). The present work was conducted to test the hypothesis that, in Chagas disease, chronic mood disorders are long-term consequences of acute T. cruzi-induced CNS inflammation. Toward this end, we used murine models and focused on tests that explore psychomotor skills and depressive-like behavior. Once a depressive phenotype was observed in T. cruzi-infected mice, we determined the abilities of the antidepressant fluoxetine and the parasiticide drug benznidazole to ameliorate depression in this model. Furthermore, because the genetic diversity of T.