The influence of congenital Toxoplasma infection on the spontaneous running activity of mice

Home-cage running-wheel activity of mice congenitally infected with Toxoplasma was recorded over 24 days. Infected mice were consistently more active than uninfected controls over the entire testing period. This finding extends previous studies and indicates that such increased activity levels occur not only in novel but also in familiar environments, and suggests that congenital toxoplasmosis tends to render mice "hyperactive'. If such behavioural alterations occur in wild mice, it is likely that infected mouse intermediate hosts would be more susceptible to predation by cats, the definitive hosts of Toxoplasma.     

Aversive stimulation and rats' preference for areas differing in novelty-value and brightness

Hooded rats were presented with black-white maze arms differing in novelty-value. Rats shocked prior to choice entered the familiar arm when this arm was black and displayed random choice when this arm was white. During an observation period following initial choice, the shocked rats that entered the familiar arm showed a greater tendency to remain in the arm initially entered than the shocked rats that entered the novel arm. The unshocked rats preferred the novel arm, irrespective of brightness, during the initial choice; this tendency was attenuated during the period following initial choice in the condition where the novel arm was also the brighter (white) alternative. The results are discussed with reference to two-factor (approach/avoidance) theories of exploratory behaviour.     

Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer's disease

Immunosuppression is a characteristic feature of Toxoplasma gondii-infected murine hosts. The present study aimed to determine the effect of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in Tg2576 AD mice. Mice were infected with a cyst-forming strain (ME49) of T. gondii, and levels of inflammatory mediators (IFN-γ and nitric oxide), anti-inflammatory cytokines (IL-10 and TGF-β), neuronal damage, and β-amyloid plaque deposition were examined in brain tissues and/or in BV-2 microglial cells. In addition, behavioral tests, including the water maze and Y-maze tests, were performed on T. gondii-infected and uninfected Tg2576 mice. Results revealed that whereas the level of IFN-γ was unchanged, the levels of anti-inflammatory cytokines were significantly higher in T. gondii-infected mice than in uninfected mice, and in BV-2 cells treated with T. gondii lysate antigen. Furthermore, nitrite production from primary cultured brain microglial cells and BV-2 cells was reduced by the addition of T. gondii lysate antigen (TLA), and β-amyloid plaque deposition in the cortex and hippocampus of Tg2576 mouse brains was remarkably lower in T. gondii-infected AD mice than in uninfected controls. In addition, water maze and Y-maze test results revealed retarded cognitive capacities in uninfected mice as compared with infected mice. These findings demonstrate the favorable effects of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of AD in Tg2576 mice.     

Estrogen receptor alpha influences socially motivated behaviors

Male mice lacking estrogen receptor alpha (ERalphaKO) show reduced social behaviors. We hypothesized that this might be due to either socially elicited or generalized anxiety. Male ERalphaKOs and wild type (WT) mice were given a series of behavioral tests: elevated plus maze, T-maze, and social recognition. Each test included a social dimension by exposing males to ovariectomized (OVX) females. In addition plasma concentrations of corticosterone were measured, and open field activity was assessed. In the elevated plus maze, WT males exposed to an OVX female 1 min prior to the test were more anxious than WT controls. ERalphaKO males showed anxiety in this test whether or not they were preexposed to a female. In the T-maze, WT males increased exploration of a novel arm when it contained an OVX female. The presence or absence of a female in a novel arm did not affect behavior of ERalphaKO males. In social recognition tests, ERalphaKO males spent less time than WT littermates investigating an OVX female that was repeatedly introduced into their home cage. On the final trial, when a novel female was introduced, WT males increased their chemo-investigation but ERalphaKOs did not. Plasma corticosterone levels were lower in ERalphaKO than in WT males when plasma was taken directly after a brief (control) cage disturbance. In the open field WT and ERalphaKO males behaved essentially the same. Taken together, the results of these experiments suggest the ERalphaKO males avoid contact with other conspecifics, perhaps due to an inability to be aroused by social cues.     

The effects of Trichinella spiralis infection on social interactions in mixed groups of infected and uninfected male mice

The presence of Trichinella spiralis infection in groups of male mice caused behavioural changes in both infected and uninfected mice. Also, for some behaviours, the extent of behavioural change in infected mice appeared to be determined by the number of muscle larvae they harboured. Infected mice showed a reduced frequency of exploratory and social behaviours compared with uninfected mice while uninfected mice performed more social investigatory activities towards those that were infected. Social interactions between infected and uninfected mice were also affected by familiarity. Behavioural differences shown to result from infection in mice familiar with each other were similar but more pronounced when the mice were unfamiliar. These results suggest that other factors may influence the behavioural effects of parasites on their hosts. For some behaviours, the greatest alterations in behaviour apparently caused by infection coincided with the period of infectivity to another host. The significance of this in relation to parasite transmission is considered.     

Cellular responses of cats with primary toxoplasmosis.

The cellular responses of 8 kittens (4 inoculated orally with mouse brains containing Toxoplasma gondii cysts and 4 uninfected controls) were studied. Oocyst numbers, body weight, and rectal temperature were monitored daily. Blood was collected weekly for serology and mononuclear cell purification. At necropsy, peritoneal and alveolar macrophages, spleen, and lymph node cells were harvested. Infected cats shed oocysts 4-15 days postinfection, maintained normal body weight and rectal temperature, and developed anti-T. gondii immunoglobulin M and G. Infected cats had normal surface immunoglobulin-positive cell populations and peripheral blood lymphocyte functions. The infected cats differed in their responses from control cats in that they developed circulating T. gondii antigen-specific lymphocytes, had increased interleukin 1 secretion by monocytes, had spleen and lymph node cells with depressed mitogenic responses and interleukin 2 production, and had macrophages with enhanced abilities in preventing the intracellular proliferation of T. gondii. Overall, the primary response of the cat to an infection with T. gondii appeared similar to that of other hosts.     

Lactation in mice fed endophyte-infected tall fescue seed

This study was conducted to assess the effects of endophyte-infected Acremonium coenophialum tall fescue (KY-31) seed (80% infected) on lactation in CD-1 dams and suckling performance of pups as measured by pup survival and growth rates. Twenty-four pairs of mature CD-1 mice were randomly allocated to four dietary treatments: 1) 100% mouse chow ad libitum; 2) 40% endophyte-infected tall fescue seed and 60% mouse chow (w/w); 3) reduced intake (100% chow), adjusted daily to the intake level of Treatment 2; and 4) 60% infected tall fescue seed and 40% chow. The mice were preconditioned on their respective diets for 100 d prior to 96 h of cohabitation between pairs of males and females. At parturition the litters were removed, and each dam was given a litter of six pups of equal weight, size and sex ratio to suckle for 15 days. All pups given to all the dams were born to other mice that were not part of the study and had not been exposed to endophyte-containing diets. Dams and litter weights were measured daily for 15 consecutive days. The combined body weight measurements of litters from dams fed the tall fescue containing diets (Treatments 2 and 4) were significantly lower (2.07 +/- 0.41 g/d) than that of litters from dams fed the chow containing diets (Treatments 1 and 3) during the suckling trial (P<0.05). Similarly, nine of ten (90%) dams fed the chow containing diets maintained five or more pups (5.5 +/- 0.2) throughout the study as compared to five of nine (55.6%) dams fed the tall fescue containing diets that maintained less than five pups (4.5 +/- 0.2).     

Gestational exposure to bisphenol A and cross-fostering affect behaviors in juvenile mice

Bisphenol-A (BPA) is a component of polycarbonate resins, and, lately, concern has been raised about its potential negative effects on human health. BPA is an estrogen analog and, in addition, it can act as a DNA hypomethylator. We examined the effects of gestational exposure to BPA on several behaviors in C57BL/6J mice. Because BPA affects maternal care, which, may have long-lasting effects on offspring behavior, we tested mice raised by either biological or fostered dams. Both diet and dam affected behavior in juvenile mice in a social novelty task and the elevated plus maze (EPM). In a social novelty task, the amount of time spent interacting with an adult male was affected by sex and gestational diet, but only in juveniles raised by a foster dam. Control females spent less time sniffing a novel adult than did control males or females exposed to BPA during gestation. In the EPM, juveniles reared by foster dams and exposed to BPA during gestation spent less time in the distal half of the open arm as compared with juveniles gestated on a control diet. Adult offspring raised by their biological dams showed the same response pattern; gestational BPA increased anxiety as compared with control diet. Our results show that prenatal BPA exposure affects social behavior and anxiety in the EPM. Moreover, some facet(s) of the infant–maternal interaction may modify these effects.     

Anticipated,Intense Risk Enhances Behavioral Conformity in a Mouse Model

A mouse conformity model was established by contrasting the differences in the time spent navigating a custom‐made maze when mice were alone versus when they were in a companion group. Experimental mice received one‐trial inhibitory avoidance training by experiencing a foot shock after they arrived at a designated goal box in the maze. In contrast, four mice of the respective companion group received food pellet trainings for rapidly approaching the same goal box. In the retest, mice receiving 0.3‐mA shock in the training trial and navigating alone displayed longer arrival latency to the goal box compared with the mice receiving same level of shock in the training trial and navigating along with the companion group. A conformity index was calculated for the arrival latency of the experimental mice receiving the retest alone and the latency of the experimental mice receiving the retest along with the companion group. In the retest, the conformity index progressively increased with the training foot shock level. No difference was noticed in the arrival latency to the goal box or the conformity index between group‐navigating experimental mice accompanied by familiar and unfamiliar groups. These results, taken together, indicate that behavioral conformity can be enhanced by an expected, intense risk. Moreover, familiarity with the companion group does not affect the behavioral conformity of an individual. We conclude that species members‐shared risk‐detecting and risk‐coping systems could be critical in motivating behavioral conformity for each member of this species.     

Effects of cold on activity and exploration by wild house mice in a residential maze

Summary Wild house mice,Mus musculus, were bred in environments kept at 23 °C (warm-reared) or 3 °C (cold-reared). Males of the fourth generation in each condition were observed for 4 days in a residential maze with a central nest box and four arms radiating from it. One maze arm contained food, one contained water, and two were empty until Day 4, when one had soft (balsa) wood. Mice of each type were run in a maze at each temperature.Mice of all classes responded to the novel environment of the maze with a high rate of visiting the arms on Day 1. The novel presence of balsa wood also provoked extra visits to the arm that contained it, and a longer stay in that arm on Day 4 than on Day 3. Visits to the arms were fewer in the cold than in the warm, and time spent in the arms was less.Cold-reared mice in the cold environment spent more time outside the nest on Day 1, that is, were more responsive to novelty than were the warmreared. Hence for the cold-reared mice the competitive balance between exploring and energy conservation was altered. This difference, we suggest, is an aspect of cold-adaptation.These experiments were done in part while JLW held an award from the National Science Foundation under the US/Australia Agreement for Scientific Cooperation. We are also grateful to Rhondda G. Dickson for help with the statistical analysis.     

Specificity of the Toxoplasma gondii-altered behaviour to definitive versus non-definitive host predation risk

The hypothesis that the parasite Toxoplasma gondii manipulates the behaviour of its intermediate rat host in order to increase its chance of being predated specifically by its feline definitive host, rather than a non-definitive host predator species, was tested. The impact of a range of therapeutic drugs, previously demonstrated to be effective in preventing the development of T. gondii-associated behavioural and cognitive alterations in rats, on definitive-host predator specificity was also tested. Using a Y-shaped maze design, we demonstrated that T. gondii-associated behavioural changes, apparently aimed to increase predation rate, do appear to be specific to that of the feline definitive host--there were significant and consistent differences between the (untreated) infected and uninfected rats groups where T. gondii-infected rats tended to choose the definitive host feline-predator-associated maze arm and nest-box significantly more often than a maze arm or nest-box treated with non-definitive host predator (mink) odour. Drug treatment of infected rats prevented any such host-specificity from being displayed. We discuss our results in terms of their potential implications both for T. gondii epidemiology and the evolution of parasite-altered behaviour.     

Induction of habits in rats by a forced-choice procedure in T-maze and the effect of pre-test free exploration

A forced-choice procedure in T-maze designed for the induction of habits was used to induce strong habits in rats. The response choices of rats in 20 free-choice trials were compared after the rats had been subjected to 1 or 200 forced-choice trials to one side of the T-maze. After 200 forced-choice trials the rats showed a significant (p < .001) propensity for the habitual arm of the maze in the subsequent free-choice trials. The habit was at least as pronounced when analysed over the last 10 free-choice trials as when it was analysed over the first 10 free-choice trials. When the rats were given the opportunity to explore the entire maze immediately before the free-choice challenge after 200 forced-choice trials, this resulted in a large variation in the choice pattern of the individual rats, and a subgroup of rats choose the newly opened maze arm in 95-100% of the 20 free-choice trials.     

Behavioral and ecological correlates of foureye butterflyfish, Chaetodon capistratus, (Perciformes: Chaetodontidae) infected with Anilocra chaetodontis (Isopoda: Cymothoidae)

We observed the behavior and ecology of Chaetodon capistratus infected and uninfected with the ectoparasitic isopod Anilocra chaetodontis to assess whether there may be parasite induced alterations in host biology, host defenses against infection, and/or pathology related to infection. We also examined habitat related differences in infection rates. Infected fish had higher rates of interaction with conspecifics and spent more time in low flow environments (which might improve transmission of juvenile parasites to new hosts). Butterfly fish without isopods were chased more frequently by damselfishes, fed more, and had larger territories. Time spent near conspecifics, and fish condition and gonadosomatic index did not vary between infected and uninfected fish. These results suggest that foureye butterfly fish behavior is altered by the isopod parasite in order for the isopods to more easily gain mates or transmit offspring to new hosts.     

Responsiveness to brightness change in hooded rats: effects of sex and procedure

In an investigation of recognition memory involving a preference test, hooded rats of both sexes were individually confined to the stem and choice area of a T- or Y-maze by means of clear Perspex barriers across each arm entrance that enabled the subjects to see into but not enter the arms. Following removal of the barriers and changing of one arm to opposite brightness, the first arm entered and the number of entries of and time spent in each arm were recorded. In the first experiment, rats entered first the arm that had been changed. During the first minute of observation, they also entered this novel arm more often and spent more time in it than the unchanged arm, irrespective of the type of change. In a second experiment, when the change was from one arm black and the other white to two black arms, more responsiveness occurred after 6-min prior exposure (without access) than after 3 min. In both experiments, the nature of the apparatus (T- or Y-maze) affected several outcomes, but the most significant influence was of the sex of the subjects. Females appeared less responsive to change than males as determined by entries of and time spent in the changed arm. Rather than inferiority of females in recognition or spatial memory, the sex effects were most likely due to their more rapid habituation to novelty possibly assisted by superior visual exploration capacities.     

Sex hormone changes induced by the parasite lead to feminization of the male host in murine Taenia crassiceps cysticercosis

Female mice are more susceptible to Taenia crassiceps (TC) infection than males. However, after a month parasite load increases massively in both genders reaching thousands of parasites per host. The possibility of hormonal changes in the infected mice was envisaged. Sex hormones levels were assayed after different periods of infection, the parasites present in the peritoneal cavity were collected and gonads, uterus and seminal vesicles were weighed. In male mice, serum estradiol increased to levels 200 times their normal values whilst those of testosterone decreased 90% relative to controls. The weight of seminal vesicles was significantly diminished. Infected female mice also showed a slight increase in estrogen blood levels after 8 weeks of infection and the weight of the uterus was significantly increased relative to controls. Serum estradiol and testosterone were almost undetectable after gonadectomy. Cytokines such as IL-6 are capable of stimulating aromatase activity and we found that splenocytes from infected mice produced amounts of IL-6 higher than control as measured by ELISA. In conclusion T. crassiceps infection triggers a feminization process in the infected hosts. The gonads are required for the parasite to induce higher estrogen synthesis. IL-6 could be involved in the immunoendocrine mechanism used by the parasite to maintain a highly permissive environment for its rapid growth.     

Human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBL SCID) models of toxoplasmosis

Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu-PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice had low titre T. gondii-specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n-glucolyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.     

Rapid Learning of Magnetic Compass Direction by C57BL/6 Mice in a 4-Armed ‘Plus’ Water Maze

Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180^° so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.     

The potential of an insect pheromone lure,Z‐7‐dodecen‐1‐yl acetate,compared with peanut butter to attract laboratory and wild rats and mice

Abstract

We compared the attractiveness to rats and mice of two lures, the pheromone Z‐7‐dodecen‐1 ‐y 1 acetate and peanut butter. In the first part of the study, laboratory‐bred rats and mice were placed in a Y‐maze. Each arm of the maze offered their normal food, plus either the pheromone or 5% ethanol as a control. There were no significant differences, by species or sex, in the number of visits or the amount of time spent in each arm. The male mice took significantly less time, however, to enter the control arm of the maze than the pheromone arm. In addition, female mice were less active during the first 5 min of the Y‐maze study than during the 5 min familiarisation period, suggesting a repellent effect of the pheromone lure. In the second part of the study, tracking tunnels were placed out in the field and baited with one of three lures—the pheromone, peanut butter or a 5% ethanol control. There was no significant difference in the number of visits by mice to tunnels containing the three lures, but rats made more visits to the tunnels containing peanut butter in the “Test” stage than in the “Neo” stage. The wild rats and mice were found not to be neophobic, suggesting the standard 3‐week familiarisation period is not necessary.     

Transmammary infection of paratenic and definitive hosts with Alaria marcianae (trematoda) mesocercariae

Transmammary infection with Alaria marcianae mesocercariae was demonstrated using mice as model, paratenic hosts. Prenatal transmission was ruled out because neonates removed immediately postpartum from infected dams were never infected. Mesocercarial distribution in virgin females and in females examined immediately postpartum showed no marked preference for the mammary glands. In contrast, infection of neonates that were allowed to suckle on infected dams was absolute, and the number of mesocercariae in the mammary glands of postparturient dams that suckled their young was increased significantly. These experimental observations were coupled with other observations on paratenic hosts to outline the pathways open to mesocercariae in gravid hosts. The term amphiparatenic host is coined for those host species that are paratenic hosts as adults, but as juveniles can serve as definitive hosts.     

Chronic Toxoplasma infection modifies the structure and the risk of host behavior

The intracellular parasite Toxoplasma has an indirect life cycle, in which felids are the definitive host. It has been suggested that this parasite developed mechanisms for enhancing its transmission rate to felids by inducing behavioral modifications in the intermediate rodent host. For example, Toxoplasma-infected rodents display a reduction in the innate fear of predator odor. However, animals with Toxoplasma infection acquired in the wild are more often caught in traps, suggesting that there are manipulations of intermediate host behavior beyond those that increase predation by felids. We investigated the behavioral modifications of Toxoplasma-infected mice in environments with exposed versus non-exposed areas, and found that chronically infected mice with brain cysts display a plethora of behavioral alterations. Using principal component analysis, we discovered that most of the behavioral differences observed in cyst-containing animals reflected changes in the microstructure of exploratory behavior and risk/unconditioned fear. We next examined whether these behavioral changes were related to the presence and distribution of parasitic cysts in the brain of chronically infected mice. We found no strong cyst tropism for any particular brain area but found that the distribution of Toxoplasma cysts in the brain of infected animals was not random, and that particular combinations of cyst localizations changed risk/unconditioned fear in the host. These results suggest that brain cysts in animals chronically infected with Toxoplasma alter the fine structure of exploratory behavior and risk/unconditioned fear, which may result in greater capture probability of infected rodents. These data also raise the possibility that selective pressures acted on Toxoplasma to broaden its transmission between intermediate predator hosts, in addition to felid definitive hosts.