Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective

Kannan, Geetha; Pletnikov, Mikhail V.

doi:10.1093/schbul/sbs079

Cited by 64 publications

(50 citation statements)

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“…In a recent study, Daniels et al indicated that spatial memory recall is impaired in rats infected with T. gondii (15). Thus, the effects of T. gondii infection on learning, memory, and emotional behavior have varied widely among different studies, although those studies used different experimental designs, which may have affected the results (36,37). We are the first to report impaired consolidation of fear memory in T. gondiiinfected mice.…”

Section: Discussionmentioning

confidence: 90%

“…The effects of T. gondii infection on rodent behavior vary with the experimental design, including differences in rodent species, route of infection, parasite strain, dosage and stage of parasites, time postinfection, and type of behavior test (36,37). These differences make it difficult to clarify the characteristics of the brain pathology associated with behavioral changes following T. gondii infection.…”

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Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

et al. 2016

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cChronic 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.T oxoplasma gondii is one of the most successful brain parasites, infecting approximately one-third of the human population (1). T. gondii can persist in brain and muscle throughout the host's life, and chronic infection is asymptomatic in immunocompetent humans (2). However, recent studies have suggested that T. gondii infection is a risk factor for developing mental diseases, such as schizophrenia and depression, as well as human behavior and personality changes and suicide (3, 4). Interestingly, T. gondii infection increases the risk of schizophrenia roughly 2.7 times, which is higher than that for genes associated with schizophrenia (5). Several studies have also suggested that rodents infected with T. gondii exhibit decreased avoidance behavior in response to cat odors, indicating manipulation of the host's behavior by T. gondii to facilitate the parasite's transmission and complete sexual replication in the definitive host (6-11).To date, research on the mechanism(s) underlying behavioral changes following T. gondii infection has been conducted primarily from two points of view. First, the relationship between parasite localization in the brain and behavioral changes has been investigated, with a previous study reporting that T. gondii has no obvious tropism in the brain (12-15). However, another study found that tissue cyst density in amygdalar areas (the medial and basolateral amygdala) is 2-fold higher than that in nonamygdalar areas (9), whereas the presence of tissue cy...

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Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

et al. 2016

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“…Similar to a number of other microbial infections, we think that both direct and indirect effects of pathogens could play a role (e.g., refs. [40][41][42]. The finding of alterations in several pathways involved in antigen processing and immune cell functioning in the hippocampus of mice exposed to ATCV-1 (Table S3 and Figs.…”

Section: Discussionmentioning

confidence: 99%

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice

Yolken

Jones‐Brando

Dunigan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

103

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Chloroviruses (family Phycodnaviridae) are large DNA viruses known to infect certain eukaryotic green algae and have not been previously shown to infect humans or to be part of the human virome. We unexpectedly found sequences homologous to the chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1) in a metagenomic analysis of DNA extracted from human oropharyngeal samples. These samples were obtained by throat swabs of adults without a psychiatric disorder or serious physical illness who were participating in a study that included measures of cognitive functioning. The presence of ATCV-1 DNA was confirmed by quantitative PCR with ATCV-1 DNA being documented in oropharyngeal samples obtained from 40 (43.5%) of 92 individuals. The presence of ATCV-1 DNA was not associated with demographic variables but was associated with a modest but statistically significant decrease in the performance on cognitive assessments of visual processing and visual motor speed. We further explored the effects of ATCV-1 in a mouse model. The inoculation of ATCV-1 into the intestinal tract of 9-11-wk-old mice resulted in a subsequent decrease in performance in several cognitive domains, including ones involving recognition memory and sensory-motor gating. ATCV-1 exposure in mice also resulted in the altered expression of genes within the hippocampus. These genes comprised pathways related to synaptic plasticity, learning, memory formation, and the immune response to viral exposure.chlorovirus ATCV-1 | infection | cognitive functioning | oropharyngeal virome | metagenomic sequencing

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“…53 Rapidly dividing tachyzoites characterize initial infection; however, 54 host immune responses eventually cause parasites to encyst in muscle 55 and nervous tissue, where they divide slowly as bradyzoites and may 56 persist for the lifetime of the organism [6]. Even during latent infection 57 in the CNS, T. gondii cysts can influence neuronal cell biology, including 58 neurotransmitter synthesis and signal transduction [8-10], as well as 59 synapse formation and dendritic arborization [11,12]. Moreover, para-60 sites elicit robust innate and TH 1 adaptive immune responses in the 61 CNS, where the expression of inflammatory cytokines, including inter-62 feron (IFN)-γ, has both protective and pathological effects [13,14].…”

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An expanded task battery in the Morris water maze reveals effects of Toxoplasma gondii infection on learning and memory in rats

Daniels

Sestito

Rouse

2015

Parasitology International

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Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective

Cited by 64 publications

References 51 publications

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice

An expanded task battery in the Morris water maze reveals effects of Toxoplasma gondii infection on learning and memory in rats

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