title: Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer's disease.
abstract: Immunosuppression is a characteristic feature of Toxoplasma gondii-infected murine hosts. The present study aimed to determine the effect of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in Tg2576 AD mice. Mice were infected with a cyst-forming strain (ME49) of T. gondii, and levels of inflammatory mediators (IFN-γ and nitric oxide), anti-inflammatory cytokines (IL-10 and TGF-β), neuronal damage, and β-amyloid plaque deposition were examined in brain tissues and/or in BV-2 microglial cells. In addition, behavioral tests, including the water maze and Y-maze tests, were performed on T. gondii-infected and uninfected Tg2576 mice. Results revealed that whereas the level of IFN-γ was unchanged, the levels of anti-inflammatory cytokines were significantly higher in T. gondii-infected mice than in uninfected mice, and in BV-2 cells treated with T. gondii lysate antigen. Furthermore, nitrite production from primary cultured brain microglial cells and BV-2 cells was reduced by the addition of T. gondii lysate antigen (TLA), and β-amyloid plaque deposition in the cortex and hippocampus of Tg2576 mouse brains was remarkably lower in T. gondii-infected AD mice than in uninfected controls. In addition, water maze and Y-maze test results revealed retarded cognitive capacities in uninfected mice as compared with infected mice. These findings demonstrate the favorable effects of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of AD in Tg2576 mice.
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Bong-Kwang
authors.initials: BK
authors.lastname: Jung
authors.forename: Kyoung-Ho
authors.initials: KH
authors.lastname: Pyo
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Shin
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Hwang
authors.forename: Hyoungsub
authors.initials: H
authors.lastname: Lim
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Sang Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
authors.forename: Jong-Yil
authors.initials: JY
authors.lastname: Chai
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Shin
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007858:Learning; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology*; D009569:Nitric Oxide / Q000378:metabolism; D014122:Toxoplasma / Q000302:isolation & purification*; D014124:Toxoplasmosis, Animal / Q000150:complications* / Q000473:pathology* / Q000821:virology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000682:Amyloid; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma