Protein expression of the tear film of domestic cats before and after inoculation with Toxoplasma gondii.

BACKGROUND: Tear film (TF) helps maintain and protect ocular function against damage to the ocular surface. Proteins are one of its main constituents, whose expression pattern can be used as a biomarker of ocular changes and systemic diseases. The aim of this study was to evaluate the expression of proteins in the TF of domestic cats before and after infection with Toxoplasma gondii, in the phases of acute infection and chronicity. Twelve healthy cats received orally homogenized brain matter obtained from mice inoculated with T. gondii oocysts, strain ME49. Cat feces were collected daily from the third day after infection to assess the release of oocysts. TF samples were obtained from cats, by Schirmer's Tear Test 1, on day 0 (before infection), day 5 after infection (acute phase of infection, with maximum peak release of oocysts in feces) and on day 21 after infection (start of chronic phase, 7 days after total absence of oocyst release in feces). Tear samples were also submitted to proteomic analysis in a Q-Tof-Premier mass spectrometer. RESULTS: A total of 37 proteins with scores equal to or greater than 100 were identified on D0, followed by 36 on D5 and 42 on D21. Of these, 27 were common to D0 and D5, 33 to D0 and D21, 27 to D5 and D21, and 26 were common to the three groups, totaling 54 proteins. The most abundant proteins were lipocalin allergen Fel d, serum albumin, aldehyde dehydrogenase, lactoperoxidase and lactotransferrin. There was no significant difference in the abundance of proteins found on D0 and D5, but there was a statistical difference between D0 and D21 for ACT1_AEDAE, CERU_HUMAN and GELS_HUMAN. Regarding D5 and D21, there were significant differences for KV1_CANLF, LAC_PIG, TRFL_PIG, ACT1_AEDAE, CERU_HUMAN, GELS_HUMAN and OVOS2_HUMAN. CONCLUSIONS: The main proteins identified in the TF of domestic cats are similar to those found in humans and other animal species. Most are part of the ocular surface defense system against injuries. The most expressed proteins in animals in the chronic phase of T. gondii infection are associated with the immune response to the parasite.

Neospora caninum and Toxoplasma gondii infections and their relationship with reproductive losses in farmed red deer (Cervus elaphus).

The aims of the present study were to determine the Neospora caninum and Toxoplasma gondii seropositivity rates in farmed red deer hinds from Argentina and their relationship with reproductive losses. Over a 2-year period, 449 hinds from 4 commercial farms were serologically tested at late gestation for N. caninum and T. gondii by IFAT. During the first year, a sequential serological analysis was carried out at 3 different time points to analyze antibody dynamics from mating until the end of the gestation period. Fetal and postnatal mortality rates were estimated by 3 successive ultrasound scannings (us) annually and a breeding control carried out after the calving period. Ultrasound fetal measurements were used to estimate conception date and gestational age of abortions. The seropositivity rate for N. caninum was 25.5% (37/145) for the yearlings and 34.2% (104/304) for the adults, while for T. gondii was 64.3% (93/145) and 78.3% (238/304), respectively. Abortions detected at us1 and us2 were 13/21 (61.9%) with a range of gestational age of 30-87 days, while abortions detected at us3 were 8/21 (38.1%) with a range of gestational age of 49-209 days. The fetal mortality rate was 4% and 5.8%, while the postnatal mortality rate was 18.8% and 4.1% of 101 yearlings and 294 adult pregnant hinds, respectively. Most seropositive hinds to both protozoans showed a stable antibody titer pattern from mating to the end of gestation, and a lower proportion developed an increase in titers suggesting infection recrudescence. Seroconversion during the gestational period was demonstrated in 6 and 50 hinds for N. caninum and T. gondii, respectively. Hinds with fetal mortality were more likely to be seropositive to N. caninum (OR = 3.1) or have N. caninum titers ≥400 (OR = 27.4) than hinds that weaned a fawn. No statistical associations were detected for T. gondii seropositivity and reproductive losses. The pregnancy rate was not affected by N. caninum or T. gondii infection, while the serological evidence of N. caninum causing postnatal mortality was marginal. Based on serological evidence, N. caninum would be a potential abortigenic agent in red deer hinds.

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

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.

Toxoplasma gondii: Effects of diphenyl diselenide in experimental toxoplasmosis on biomarkers of cardiac function.

This study aimed to investigate the effects of diphenyl diselenide (PhSe)2 to treat mice experimentally infected by Toxoplasma gondii on seric biomarkers of cardiac function (creatine kinase, creatine kinase MB, troponin, and myoglobin), and lactate dehydrogenase, as well as to evaluate the enzymatic activity of creatine kinase (CK) and adenylate kinase (AK) in heart tissue. For the study, 40 female mice were divided into four groups of 10 animals each: the group A (uninfected and untreated), the group B (uninfected and treated), the group C (infected and untreated) and the group D (infected and treated). The inoculation was performed with 50 cysts of T. gondii (ME-49 strain). Mice from groups B and D were treated at days 1 and 20 post-infection (PI) with 5 µmol kg(-1) of (PhSe)2 subcutaneously. On day 30 PI, the mice were anesthetized and euthanized for blood and heart collection. As a result, it was observed a decrease in AK activity (P < 0.01) in the heart samples of groups C and D compared to the group A. Cardiac CK increased in the group C compared to the group A (P < 0.01). CK levels increased in infected mice (the group C) compared to other groups (A and D). Regarding CK-MB level, there was a decrease in the group D compared to the group B, without statistical difference compared to control groups (A and C). It was observed an increase on myoglobin in groups C and D, differently of troponin, which did not show statistical difference (P < 0.05) between groups. Mice from the group C showed an increase in lactate dehydrogenase (LDH) levels compared to other groups (A, B, and D). Histopathological evaluation of heart samples revealed necrosis, hemorrhagic regions and inflammatory infiltrates in mice from the Group C, differently from the group D where animals showed only inflammatory infiltrates. Based on these results we conclude that the (PhSe)2 had a protective effect on the heart in experimental toxoplasmosis by modulating tissue and seric CK activity, and avoiding an increase on seric LDH levels, probably due to the antioxidant effect of this compound.

Diphenyl diselenide supplementation in infected mice by Toxoplasma gondii: Protective effect on behavior, neuromodulation and oxidative stress caused by disease.

The aim of this study was to evaluate the effect of subcutaneous administration of diphenyl diselenide (PhSe)2 on animal behavior and activities of acetylcholinesterase (AChE), adenylate kinase (AK), and creatine kinase (CK) in the brain of mice infected by Toxoplasma gondii. In addition, thiobarbituric acid reactive species (TBARS) levels and glutathione (GR, GPx and GST) activity were also evaluated. For the study, 40 female mice were divided into four groups of 10 animals each: group A (uninfected and untreated), group B (uninfected and treated with (PhSe)2), group C (infected and untreated) and group D (infected and treated with (PhSe)2). The mice were inoculated with 50 cysts of the ME49 strain of T. gondii. After infection the animals of the groups B and D were treated on days 1 and 20 post-infection (PI) with 5.0 µmol/kg of (PhSe)2 subcutaneously. Behavioral tests were conducted on days 29 PI to assess memory loss (object recognition), anxiety (elevated plus maze), locomotor and exploratory activity (Open Field) and it was found out that infected and untreated animals (group C) had developed anxiety and memory impairment, and the (PhSe)2 treatment did not reverse these behavioral changes on infected animals treated with (PhSe)2 (group D). The results showed an increase on AChE activity (P < 0.01) in the brain of infected and untreated animals (group C) compared to the uninfected and untreated animals (group A). The AK and CK activities decreased in infected and untreated animals (group C) compared to the uninfected and untreated animals (group A) (P < 0.01), however the (PhSe)2 treatment did not reverse these alterations. Infected and untreated animals (group C) showed increased TBARS levels and GR activity, and decreased GPx and GST activities when compared to uninfected and untreated animals (group A). Infected animals treated with (PhSe)2 (group D) decreased TBARS levels and GR activity, while increased GST activity when compared to infected and untreated animals (group C). It was concluded that (PhSe)2 showed antioxidant activity, but the dose used had no anti-inflammatory effect and failed to reverse the behavioral changes caused by the parasite.

Infection of male rats with Toxoplasma gondii results in enhanced delay aversion and neural changes in the nucleus accumbens core.

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.

NLRP1 is an inflammasome sensor for Toxoplasma gondii.

The obligate intracellular parasite Toxoplasma gondii is able to infect nearly all nucleated cell types of warm-blooded animals. This is achieved through the injection of hundreds of parasite effectors into the host cell cytosol, allowing the parasite to establish a vacuolar niche for growth, replication, and persistence. Here we show that Toxoplasma infection actives an inflammasome response in mice and rats, an innate immune sensing system designed to survey the host cytosol for foreign components leading to inflammation and cell death. Oral infection with Toxoplasma triggers an inflammasome response that is protective to the host, limiting parasite load and dissemination. Toxoplasma infection is sufficient to generate an inflammasome response in germfree animals. Interleukin 1ß (IL-1ß) secretion by macrophage requires the effector caspases 1 and 11, the adapter ASC, and NLRP1, the sensor previously described to initiate the inflammasome response to Bacillus anthracis lethal factor. The allele of NLRP1b derived from 129 mice is sufficient to enhance the B6 bone marrow-derived macrophage (BMDM) inflammasome response to Toxoplasma independent of the lethal factor proteolysis site. Moreover, N-terminal processing of NLRP1b, the only mechanism of activation known to date, is not observed in response to Toxoplasma infection. Cumulatively, these data indicate that NLRP1 is an innate immune sensor for Toxoplasma infection, activated via a novel mechanism that corresponds to a host-protective innate immune response to the parasite.

Neospora caninum infection as a cause of reproductive failure in a sheep flock.

Neospora caninum has been detected only sporadically in cases of ovine abortion, and it has therefore traditionally been considered as an unimportant parasite in small ruminants. This study was carried out with the aim of identifying the pathogen causing serious reproductive problems on a commercial sheep farm. Sera from all rams and ewes tested negative for antibodies against Border disease virus, Schmallenberg virus and Coxiella burnetii, and infections by these agents were therefore ruled out. Nevertheless, seropositivity to N. caninum and/or Toxoplasma gondii was detected, although the seroprevalence was higher in the case of N. caninum. The percentage of lambings and the number of lambs per dam were significantly lower in ewes that were seropositive to N. caninum while no effect on these parameters was detected in ewes that were seropositive to T. gondii. There was also no evidence of infection by T. gondii in the foetal/lamb tissues analyzed by PCR and/or immunohistopathological techniques. On the contrary, the DNA of N. caninum was detected in 13 out of 14 foetuses/lambs descendant from dams seropositive to this parasite. Characteristic lesions caused by N. caninum and/or its antigen were also detected. Genotyping of the N. caninum DNA revealed only two closely related microsatellite multilocus genotypes. The results clearly demonstrate that infection by N. caninum was the cause of the low reproductive performance of this sheep flock.

Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour?

We examine the role of the protozoan Toxoplasma gondii as a manipulatory parasite and question what role study of infections in its natural intermediate rodent hosts and other secondary hosts, including humans, may elucidate in terms of the epidemiology, evolution and clinical applications of infection. In particular, we focus on the potential association between T. gondii and schizophrenia. We introduce the novel term 'T. gondii-rat manipulation-schizophrenia model' and propose how future behavioural research on this model should be performed from a biological, clinical and ethically appropriate perspective.

Toxoplasma gondii infection and behaviour - location, location, location?

Parasite location has been proposed as an important factor in the behavioural changes observed in rodents infected with the protozoan Toxoplasma gondii. During the chronic stages of infection, encysted parasites are found in the brain but it remains unclear whether the parasite has tropism for specific brain regions. Parasite tissue cysts are found in all brain areas with some, but not all, prior studies reporting higher numbers located in the amygdala and frontal cortex. A stochastic process of parasite location does not, however, seem to explain the distinct and often subtle changes observed in rodent behaviour. One factor that could contribute to the specific changes is increased dopamine production by T. gondii. Recently, it was found that cells encysted with parasites in the brains of experimentally infected rodents have high levels of dopamine and that the parasite encodes a tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of this neurotransmitter. A mechanism is proposed that could explain the behaviour changes due to parasite regulation of dopamine. This could have important implications for T. gondii infections in humans.

Sex-dependent neurotransmitter level changes in brains of Toxoplasma gondii infected mice.

The protozoan parasite Toxoplasma gondii has the ability to alter intermediate host behavior, most impressively the natural aversion to cat scent, to favor the predation by the definitive host. However, the underlying mechanism of the observed phenomenon still remains unknown. Since changes in the neurotransmitter level are postulated as a possible contributing factor, the aim of this work was to assess the monoamine systems activity in specified brain regions involved in the natural defense behaviors, emotion evaluation, and motor and sensory stimuli integration in experimentally T. gondii infected mice compared to uninfected controls. Taking into account the natural differences between genders, the experiments were carried out on both male and female mice. Our results revealed statistically significant changes in all tested monoamine systems with regard to both gender and time after T. gondii invasion. Acute toxoplasmosis was accompanied by a decrease in noradrenergic system activity in females and its slight increase in some brain areas of males. Acute invasion also induced a rise in serotonin system activity, mostly in males. The most striking observation was an increase in the dopamine release noted in acutely infected males. We discuss our results in terms of their possible contribution to T. gondii-induced intermediate host behavior alterations and parasite transmission and with regard to postulated relationship between T. gondii seroprevalence and occurrence of certain disorders such as schizophrenia in humans.

Pulmonary exposure to single-walled carbon nanotubes does not affect the early immune response against Toxoplasma gondii.

BACKGROUND: Single-walled carbon nanotubes (SWCNT) trigger pronounced inflammation and fibrosis in the lungs of mice following administration via pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational setting may occur in conjunction with infections and this could yield enhanced or suppressed responses to the offending agent. Here, we studied whether the sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with the ubiquitous intracellular parasite Toxoplasma gondii would impact on the immune response of the host against the parasite. METHODS: C57BL/6 mice were pre-exposed by pharyngeal administration of SWCNT (80 + 80 µg/mouse) for two consecutive days followed by intravenous injection with either 1x103 or 1x104 green fluorescence protein and luciferase-expressing T. gondii tachyzoites. The dissemination of T. gondii was monitored by in vivo bioluminescence imaging in real time for 7 days and by plaque formation. The inflammatory response was analysed in bronchoalveolar lavage (BAL) fluid, and by assessment of morphological changes and immune responses in lung and spleen. RESULTS: There were no differences in parasite distribution between mice only inoculated with T. gondii or those mice pre-exposed for 2 days to SWCNT before parasite inoculum. Lung and spleen histology and inflammation markers in BAL fluid reflected the effects of SWCNT exposure and T. gondii injection, respectively. We also noted that CD11c positive dendritic cells but not F4/80 positive macrophages retained SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization of T. gondii with CD11c or F4/80 positive cells could not be observed in lungs or spleen. Pre-exposure to SWCNT did not affect the splenocyte response to T. gondii. CONCLUSIONS: Taken together, our data indicate that pre-exposure to SWCNT does not enhance or suppress the early immune response to T. gondii in mice.

Oxidative stress and tryptophan degradation pattern of acute Toxoplasma gondii infection in mice.

Toxoplasma gondii is a very common obligate single-cell protozoan parasite which induces overproduction of interferon (IFN)-gamma and of other proinflammatory cytokines. Although immunomodulatory role of IFN-gamma favors tryptophan (Trp) degradation via indoleamine-2,3-dioxygenase (IDO) activity and is related with nitric oxide (NO) synthesis, the mechanism of antitoxoplasma activity is complex. In order to characterize the Trp degradation pattern during the acute T. gondii infection, serum Trp, kynurenine (Kyn), and urinary biopterin levels of mice were measured. The possible oxidative status was evaluated by the liver, spleen, brain, and serum malondialdehyde (MDA) and NO levels. Increased free radical toxicity may cause elevation in tissue MDA in T. gondii-infected mice, while unchanged serum MDA might indicate the increased oxidative stress due to T. gondii infection restricted to intracellular area. Elevated serum NO most probably might be due to the formation of reactive nitrogen radicals. The Kyn/Trp ratio was higher in T. gondii-infected mice compared to healthy animals (p < 0.05); however, it was not correlated with urinary biopterin. These results suggested that Trp degradation might be promoted by a pathway other than IDO during T. gondii infection and the reduction of Trp concentration favors the local immunosuppression and systemic tolerance.

Behavioral changes in mice caused by Toxoplasma gondii invasion of brain.

Toxoplasma gondii, a protozoan parasite, is capable of infecting a broad range of intermediate warm-blooded hosts including humans. The parasite undergoes sexual reproduction resulting in genetic variability only in the intestine of the definitive host (a member of the cat family). The parasite seems to be capable of altering the natural behavior of the host to favor its transmission in the environment. The aim of this study was to evaluate the number of parasite cysts formed in the hippocampus and amygdala of experimentally infected mice as these regions are involved in defense behaviors control and emotion processing, and to assess the influence of the infection on mice behavior. The obtained results revealed the presence of parasite cysts both in the hippocampus and the amygdala of infected mice; however, no clear region-dependent distribution was observed. Furthermore, infected mice showed significantly diminished exploratory activity described by climbing and rearing, smaller preference for the central, more exposed part of the OF arena and engaged in less grooming behavior compared to uninfected controls.

Toxoplasma gondii: the effects of infection at different stages of pregnancy on the offspring of mice.

Congenital toxoplasmosis can cause fetal damage in humans and domestic animals. This study was focused on the effects of Toxoplasma gondii (Prugniaud strain) infection at different stages of pregnancy on the offspring of mice. Results showed that newborn mice from all infected groups were significantly lower in weight than those from the control group but significant difference was not found among these groups at day 60 after birth. The survival rate of the offspring from the group of mice infected at the earlier stage of pregnancy was significantly lower than those of infected and control groups. The positive offspring (with cysts found in their brain tissues) born from the mice infected at the earlier and intermediate stages of pregnancy showed a shorter latency and greater number of errors in the step-through passive avoidance test than those born from the mice infected at the late stage of pregnancy, the control group and the negative offspring from the infected groups. The number of cysts in the brain tissue was significantly higher in the offspring born from the groups of mice infected at the earlier and intermediate stages of pregnancy than those from the group of mice infected at the late stage of pregnancy. In addition, our results indicated that a high congenital transmission rate (90%) occurred in this NIH mouse model. In conclusion, the earlier and intermediate maternal infection of T. gondii can result in severe congenital toxoplasmosis, exhibiting conditions such as stillbirth or non-viability, and learning or memory capability damage in this mouse model. These results not only provide useful data for better understanding the effects of T. gondii infection on the offspring of mice infected at different stages of pregnancy but also for better consideration of the effect of this infection on other mammalian hosts including humans.

Behavioral Manipulation by Toxoplasma gondii: Does Brain Residence Matter?

The protozoan parasite Toxoplasma gondii infects a wide range of intermediate hosts. The parasite produces brain cysts during the latent phase of its infection, in parallel to causing a loss of innate aversion in the rat host towards cat odors. Host behavioral change presumably reflects a parasitic manipulation to increase predation by definitive felid hosts, although evidence for increased predation is not yet available. In this opinion piece, we propose a neuroendocrine loop to explain the role of gonadal steroids in the parasitized hosts in mediating the behavioral manipulation. We argue that the presence of tissue cysts within the host brain is merely incidental to the behavioral change, without a necessary or sufficient role.

Behavioral biology of Toxoplasma gondii infection.

Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a variety of intermediate hosts through a combination of carnivory and vertical transmission. However, T. gondii produces gametes only in felids after the predation of infected intermediate hosts. The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. Here, we provide a short description of such parasitic behavioral manipulation in laboratory rodents infected with T. gondii, along with a bird's eye view of underpinning biological changes in the host. We also summarize critical gaps and opportunities for future research in this exciting research area with broad implications in the transdisciplinary study of host-parasite relationships.

Manipulation of host behaviour by Toxoplasma gondii: what is the minimum a proposed proximate mechanism should explain?

The behavioural manipulation hypothesis posits that parasites can change the behaviour of hosts to increase the reproductive fitness of the parasite. The protozoan parasite Toxoplasma gondii fits this description well. Sexual reproduction occurs in the cat intestine, from which highly stable oocysts are excreted in faeces. Grazing animals, including rodents, can then ingest these oocysts. The parasite has evolved the capacity to abolish the innate fear that rodents have of the odours of cats, and to convert that fear into an attraction. This presumably increases the likelihood of the rodent being predated, thereby completing the parasite's life cycle. The behavioural syndrome produced by T. gondii does not have any precedent in neuroscience research. This is not a case where the normal functioning of fear system have been altered. This is not even the case of the altering of fear towards predator odours, while leaving other kinds of fear intact. This is an unprecedented example of one component of the fear being eliminated (and replaced by a novel attraction), while appearing to leave other domains unchanged. An understanding of the neurobiological effects of T. gondii is beginning to emerge. One possibility is T. gondii's preferential localisation to, and effects within the amygdala; this is particularly intriguing, given the role of this brain structure in the normal fear response. Obviously, far more must be understood, and the unique behavioural effects of T. gondii put very demanding constraints on any hypothesis we formulate to explain proximate neurobiological mechanisms.

Latent Toxoplasmosis Effects on Rodents and Humans: How Much is Real and How Much is Media Hype?

Toxoplasma gondii is a ubiquitous, intracellular protozoan parasite with a broad range of intermediate hosts, including humans and rodents. In many hosts, T. gondii establishes a latent long-term infection by converting from its rapidly dividing or lytic form to its slowly replicating and encysting form. In humans and rodents, the major organ for encystment is the central nervous system (CNS), which has led many to investigate how this persistent CNS infection might influence rodent and human behavior and, more recently, neurodegenerative diseases. Given the interest in this topic, here we seek to take a global approach to the data for and against the effects of latent T. gondii on behavior and neurodegeneration and the proposed mechanisms that might underlie behavior modifications.

Neuropsychiatric disease and Toxoplasma gondii infection.

Toxoplasma gondii infects approximately 30% of the world's population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed.