Patterns of Toxoplasma gondii cyst distribution in the forebrain associate with individual variation in predator odor avoidance and anxiety-related behavior in male Long–Evans rats

Evans, Andrew K.; Strassmann, Patrick S.; Lee, I-Ping; Sapolsky, Robert M.

doi:10.1016/j.bbi.2013.11.012

Cited by 77 publications

(70 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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). Here, our histopathological analysis showed that meningitis in the cortex was more severe than that in other regions.…”

Section: Discussionsupporting

confidence: 81%

“…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). Overall, these studies suggest that the T. gondii cyst distribution contributes to behavioral changes, but this still requires further investigation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2016

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In contrast, many studies have demonstrated that adult rats are one of the most resistant hosts to T. gondii infection with respect to clinical toxoplasmosis and this phenomenon has been known for more than half a century (Benedetto et al, 1996;Evans et al, 2014;Fujii et al, 1983;Lewis and Markell, 1958;Li et al, 2012;Nakayama and Hoshiai, 1960). The similarity between the clinical course in rat and human toxoplasmosis suggests the use of rats as an ideal model to elucidate the mechanism of Toxoplasma infection in humans (Darcy and Zenner, 1993;Santoro et al, 1987;Zenner et al, 1998Zenner et al, , 1999aZenner et al, , 1999b.…”

Section: Introductionmentioning

confidence: 82%

Investigation of infectivity of neonates and adults from different rat strains to Toxoplasma gondii Prugniaud shows both variation which correlates with iNOS and Arginase-1 activity and increased susceptibility of neonates to infection

Gao

et al. 2015

Experimental Parasitology

View full text Add to dashboard Cite

Mouse models differ considerably from humans with regard to clinical symptoms of toxoplasmosis caused by Toxoplasma gondii and, by comparison, the rat model is more representative of this disease in humans. In the present study, we found that different strains of adult and newborn rats (Lewis, Wistar, Sprague Dawley, Brown Norway and Fischer 344) exhibited remarkable variation in the number of brain cysts following inoculation with the T.gondii Prugniaud strain. In adult rats, large numbers of cysts (1231 ± 165.6) were observed in Fischer 344, but none in the other four. This situation was different in newborn rats aged from 5 to 20 days old. All Fischer 344 and Brown Norway newborns were cyst-positive while cyst-positive infection in Sprague Dawley neonates ranged from 54.5% to 60% depending on their age at infection. In Wistar and Lewis rat neonates, however, cyst-positivity rates of 0-42.9% and 0-25% were found respectively. To investigate whether rat strain differences in infectivity could be related to inherent strain and genetic differences in the host immune response, we correlated our data with previously reported strain differences in iNOS/Arginase ratio in adult rats and found them to be linked. These results show that interactions between host genetic background and age of rat influence T.gondii infection.

show abstract

“…Mechanisms of such anatomically restricted changes remain presently unknown. It has earlier been suggested that T. gondii preferentially concentrates in certain brain regions, and this tropism can explain behavioural changes post-infection through local manipulation of neuronal signalling and/or damage [2,46,47]. Two early studies in this regard reported a rather widespread occurrence of tissues cysts in a variety of brain regions [2,47].…”

Section: Discussionmentioning

confidence: 99%

Infection of male rats withToxoplasma gondiiresults in enhanced delay aversion and neural changes in the nucleus accumbens core

et al. 2015

View full text Add to dashboard Cite

Rats infected with the protozoan parasite Toxoplasma gondii exhibit reduced avoidance of predator odours. This behavioural change is likely to increase transmission of the parasite from rats to cats. Here, we show that infection with T. gondii increases the propensity of the infected rats to make more impulsive choices, manifested as delay aversion in an intertemporal choice task. Concomitantly, T. gondii infection causes reduction in dopamine content and neuronal spine density of the nucleus accumbens core, but not of the nucleus accumbens shell. These results are consistent with a role of the nucleus accumbens dopaminergic system in mediation of choice impulsivity and goal-directed behaviours. Our observations suggest that T. gondii infection in rats causes a syndromic shift in related behavioural constructs of innate aversion and making foraging decisions.

show abstract

Patterns of Toxoplasma gondii cyst distribution in the forebrain associate with individual variation in predator odor avoidance and anxiety-related behavior in male Long–Evans rats

Cited by 77 publications

References 52 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

Investigation of infectivity of neonates and adults from different rat strains to Toxoplasma gondii Prugniaud shows both variation which correlates with iNOS and Arginase-1 activity and increased susceptibility of neonates to infection

Infection of male rats withToxoplasma gondiiresults in enhanced delay aversion and neural changes in the nucleus accumbens core

Contact Info

Product

Resources

About