title: Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.
abstract: Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, 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, Obihiro, Hokkaido, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Yoshikage
authors.initials: Y
authors.lastname: Muroi
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
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, Obihiro, Hokkaido, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagamune
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000679:Amygdala / Q000469:parasitology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D002540:Cerebral Cortex / Q000469:parasitology / Q000503:physiopathology*; D002851:Chromatography, High Pressure Liquid; D005239:Fear / Q000502:physiology*; D008297:Male; D000069077:Memory Consolidation / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000469:parasitology* / Q000503:physiopathology; D059208:Parasite Load; D014122:Toxoplasma / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000469:parasitology / Q000503:physiopathology
chemical_list: D015415:Biomarkers