Behavioral changes in mice caused by Toxoplasma gondii invasion of brain

Gatkowska, Justyna; Wieczorek, Marek; Dziadek, Bożena; Dzitko, Katarzyna; Długońska, Henryka

doi:10.1007/s00436-011-2800-y

Cited by 84 publications

(64 citation statements)

References 29 publications

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“…Furthermore, real-time PCR was used to determine the expression of SAG1, BAG1, and GRA1 in the brain tissues and showed that neither the expression of the bradyzoite marker nor the low level of expression of SAG1 was specific to any particular brain region, suggesting that there was no cyst tropism. Consistent with the findings of previous studies in mice, T. gondii had no obvious preference for specific brain regions (12)(13)(14). In addition, no other study has reported clear evidence to support the idea that parasite localization plays a critical role in the behavioral changes induced by T. gondii infection (9,15,16,43).…”

Section: Discussionsupporting

confidence: 88%

“…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)(13)(14)(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 cysts in the forebrain contributes to the attenuation of predator odor aversion and anxiety-like behavior (16).…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 88%

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confidence: 99%

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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“…Hence, it is essential to prove that the strain used in this study, Pru⌬ku80⌬hxg, induces an increase in dopamine prior to gene knockout studies. An increase in dopamine in brains of infected mice was also not reproduced as in previously published studies (3)(4)(5). Furthermore, Wang et al used a different outbred mouse line for their in vivo study than that reported by Prandovszky at al.…”

mentioning

confidence: 80%

“…Prior work has found altered dopamine neurotransmission with T. gondii infection (2)(3)(4)(5). In the study of Wang et al, dopaminergic PC12 cell cultures were incubated at alkaline pH to examine dopamine levels in bradyzoite-infected cells, a standard procedure used to induce parasite conversion in fibroblasts, yet the synthesis of dopamine in PC12 cells is sensitive to pH changes (6).…”

mentioning

confidence: 99%

Reproducing Increased Dopamine with Infection To Evaluate the Role of Parasite-Encoded Tyrosine Hydroxylase Activity

McConkey

Peers

Prandovszky³

2015

Infect Immun

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“…Few studies have also described impaired sensorimotor functions, which manifested in the form of poor performance in grip strength and balance beam tests, diminished exploratory activity and gait alterations, but involvement of the spinal cord was not addressed [31,32]. All together, these observations suggest that spinal cord pathology should receive increased attention similar to brain pathology, to further elucidate the behavioral changes in mice caused by T. gondii infection.…”

Section: Introductionmentioning

confidence: 99%

Spinal cord pathology in chronic experimentalToxoplasma gondiiinfection

Möhle¹,

Parlog²,

Pahnke³

et al. 2014

European Journal of Microbiology and Immunology

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Infection with the protozoan Toxoplasma (T.) gondii causes chronic infection of the central nervous system and can lead to lifethreatening encephalomyelitis in immunocompromised patients. While infection with T. gondii has long time been considered asymptomatic in immunocompetent hosts, this view is challenged by recent reports describing links between seropositivity and behavioral alterations.However, past and current researches are mainly focused on the brain during Toxoplasma encephalitis, neglecting the spinal cord as a key structure conveying brain signals into motion. Therefore, our study aimed to fill the gap and describes the spinal cord pathology in an experimental murine model of toxoplasmosis.In the spinal cord, we found distinct histopathological changes, inflammatory foci and T. gondii cysts similar to the brain. Furthermore, the recruitment of immune cells from the periphery was detected. Moreover, resident microglia as well as recruited monocytes displayed an increased MHC classes I and II expression. Additionally, the expression of pro-and anti-inflammatory cytokines was enhanced in the brain as well as in the spinal cord. In summary, the pathology observed in the spinal cord was similar to the previously described changes in the brain during the infection.This study provides the first detailed description of histopathological and immunological alterations due to experimental T. gondii induced myelitis in mice. Thus, our comparison raises awareness of the importance of the spinal cord in chronic T. gondii infection.

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Behavioral changes in mice caused by Toxoplasma gondii invasion of brain

Cited by 84 publications

References 29 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

Reproducing Increased Dopamine with Infection To Evaluate the Role of Parasite-Encoded Tyrosine Hydroxylase Activity

Spinal cord pathology in chronic experimentalToxoplasma gondiiinfection

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