title: Involvement of Host Defense Mechanisms against Toxoplasma gondii Infection in Anhedonic and Despair-Like Behaviors in Mice.
abstract: Toxoplasma gondiiis a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronicT. gondiiinfection induced depression-like behaviors in mice. Furthermore, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2,3-dioxygenase (IDO), inflammation, and interferon gamma (IFN-γ) to anhedonic and despair-related behaviors inT. gondii-infected mice by using sucrose preference and forced-swim tests, respectively. First, we confirmed that BALB/c mice exhibited both sickness and depression-like behaviors during acute infection. Treatment of infected wild-type mice with minocycline (anti-inflammatory drug) abated sickness and anhedonic and despair-like behaviors, whereas inT. gondii-infected mice, treatment normalized kynurenine/tryptophan (Kyn/Trp) ratios in both plasma and brain tissue. Additionally,T. gondiiinfection failed to induce anhedonic and despair-like behaviors or increase the Kyn/Trp ratio in immunocompromised (IFN-γ-/-) mice, whereas sickness behavior was observed in both immunocompetent and IFN-γ-/-mice following infection. Furthermore, treatment with 1-methyl tryptophan (an IDO inhibitor) did not affect locomotor activity, attenuated clinical scores and anhedonic and despair-like behaviors, and resulted in normal Kyn/Trp ratios inT. gondii-infected wild-type mice. Although low levels of serotonin and dopamine were observed in the brain during acute and chronic infections, anhedonic and despair-like behaviors were not detected in the chronic stage of infection. Collectively, our results demonstrated that immune enhancement in response to infection withT. gondiiresulted in IFN-γ production, IDO activation, and inflammation associated with anhedonic and despair-like behaviors.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.|Department of Animal Behavior, Management, Genetics and Breeding, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.
authors.forename: Motamed Elsayed
authors.initials: ME
authors.lastname: Mahmoud
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.
authors.forename: Ragab
authors.initials: R
authors.lastname: Fereig
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D059445:Anhedonia; D000818:Animals; D001522:Behavior, Animal; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D007371:Interferon-gamma
keywords: 1-methyl tryptophan; Toxoplasma gondii; anhedonic behavior; despair-like behavior; interferon gamma; minocycline; sickness behavior