title: Induction of depression-related behaviors by reactivation of chronic Toxoplasma gondii infection in mice.
abstract: Although Toxoplasma gondii (T. gondii) infection is relevant to many psychiatric disorders, the fundamental mechanisms of its neurobiological correlation with depression are poorly understood. Here, we show that reactivation of chronic infection by an immunosuppressive regimen caused induction of depressive-like behaviors without obvious sickness symptoms. However, the depression-related behaviors in T. gondii-infected mice, specifically, reduced sucrose preference and increased immobility in the forced-swim test were observed at the reactivation stage, but not in the chronic infection. Interestingly, reactivation of T. gondii was associated with production of interferon-gamma and activation of brain indoleamine 2, 3-dioxygenase, which converts tryptophan to kynurenine and makes it unavailable for serotonin synthesis. Furthermore, serotonin turnover to its major metabolite, 5-hydroxyindoleacetic acid, was also enhanced at the reactivation stage. Thus, enhanced tryptophan catabolic shunt and serotonin turnover may be implicated in development of depressive-like behaviors in mice with reactivated T. gondii.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan; Department of Animal Behavior, Management, Genetics and Breeding, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, 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 080-8555, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ihara
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Ragab M
authors.initials: RM
authors.lastname: Fereig
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. Electronic address: nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002908:Chronic Disease; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology*; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004327:Drinking Behavior; D005260:Female; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009043:Motor Activity; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000150:complications / Q000503:physiopathology* / Q000523:psychology*
chemical_list: D019422:Dietary Sucrose; C583637:IDO1 protein, mouse; C586429:IDO2 protein, mouse; C587672:IL1B protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053583:Interleukin-1beta; D012701:Serotonin; D007737:Kynurenine; D007371:Interferon-gamma; D004298:Dopamine; D009638:Norepinephrine
keywords: 3 dioxygenase; Depressive-like behaviors; Indoleamine 2; Mouse; Reactivation; Toxoplasma gondii