BACKGROUND: The highly prevalent parasite Toxoplasma gondii reportedly manipulates rodent behavior to enhance the likelihood of transmission to its definitive cat host. The proximate mechanisms underlying this adaptive manipulation remain largely unclear, though a growing body of evidence suggests that the parasite-entrained dysregulation of dopamine metabolism plays a central role. Paradoxically, the distribution of the parasite in the brain has received only scant attention. METHODOLOGY/PRINCIPAL FINDINGS: The distributions of T. gondii cysts and histopathological lesions in the brains of CD1 mice with latent toxoplasmosis were analyzed using standard histological techniques. Mice were infected per orally with 10 tissue cysts of the avirulent HIF strain of T. gondii at six months of age and examined 18 weeks later. The cysts were distributed throughout the brain and selective tropism of the parasite toward a particular functional system was not observed. Importantly, the cysts were not preferentially associated with the dopaminergic system and absent from the hypothalamic defensive system. The striking interindividual differences in the total parasite load and cyst distribution indicate a probabilistic nature of brain infestation. Still, some brain regions were consistently more infected than others. These included the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, and, importantly, the hippocampus and the amygdala. By contrast, a consistently low incidence of tissue cysts was recorded in the cerebellum, the pontine nuclei, the caudate putamen and virtually all compact masses of myelinated axons. Numerous perivascular and leptomeningeal infiltrations of inflammatory cells were observed, but they were not associated with intracellular cysts. CONCLUSION/SIGNIFICANCE: The observed pattern of T. gondii distribution stems from uneven brain colonization during acute infection and explains numerous behavioral abnormalities observed in the chronically infected rodents. Thus, the parasite can effectively change behavioral phenotype of infected hosts despite the absence of well targeted tropism.

• MeSH
• biologické modely MeSH
• chování zvířat MeSH
• chronická nemoc MeSH
• dopamin metabolismus   MeSH
• kočky MeSH
• kontrola chování MeSH
• mozek parazitologie   patologie   MeSH
• myši MeSH
• orgánová specificita MeSH
• počet buněk MeSH
• tělesná hmotnost fyziologie   MeSH
• Toxoplasma cytologie   fyziologie   MeSH
• toxoplazmóza parazitologie   patologie   MeSH
• tropismus fyziologie   MeSH
• velikost buňky MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The parasitic protozoan Toxoplasma gondii infects about one-third of the population of developed countries. The life-long presence of dormant stages of this parasite in the brain and muscular tissues of infected humans is usually considered asymptomatic from the clinical point of view. In the past 20 years, research performed mostly on military personnel, university students, pregnant women and blood donors has shown that this 'asymptomatic' disease has a large influence on various aspects of human life. Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two versions of Cattell's 16PF, Cloninger's TCI and Big Five questionnaires. Most of these differences increase with the length of time since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control study. Latent toxoplasmosis is associated with immunosuppression, which might explain the increased probability of giving birth to a boy in Toxoplasma-infected women and also the extremely high prevalence of toxoplasmosis in mothers of children with Down syndrome. Toxoplasma-infected male students are about 3 cm taller than Toxoplasma-free subjects and their faces are rated by women as more masculine and dominant. These differences may be caused by an increased concentration of testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the disease. Finally, five independent studies performed in blood donors, pregnant women and military personnel showed that RhD blood group positivity, especially in RhD heterozygotes, protects infected subjects against various effects of latent toxoplasmosis, such as the prolongation of reaction times, an increased risk of traffic accidents and excessive pregnancy weight gain. The modern human is not a natural host of Toxoplasma. Therefore, it can only be speculated which of the observed effects of latent toxoplasmosis are the result of the manipulation activity of the Toxoplasma aimed to increase the probability of its transmission from a natural intermediate to the definitive host by predation, and which are just side effects of chronic infection.

• MeSH
• chování MeSH
• fenotyp MeSH
• interakce hostitele a parazita * MeSH
• lidé MeSH
• osobnost * MeSH
• reakční čas MeSH
• schizofrenie etiologie   parazitologie   MeSH
• těhotenství MeSH
• Toxoplasma fyziologie   MeSH
• toxoplazmóza epidemiologie   patologie   patofyziologie   psychologie   MeSH
• velikost těla MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: A high seizure threshold (ST) is an impeding factor in certain patients, potentially preventing a successful electroconvulsive therapy (ECT) treatment. Several pharmacological and non-pharmacological methods have been put forward to augment ECT in such patients, however, to this date, only a handful of case reports existed about the potential role of repetitive transcranial magnetic stimulation (rTMS), as an augmentation method. OBJECTIVES: and Methods: In this randomized, double-blinded, sham controlled study, we set out to test the hypothesis of whether the application of high frequency transcranial magnetic stimulation (HF rTMS) lowers the seizure threshold for electroconvulsive therapy and whether it has an effect on other aspects of ECT treatment, such as seizure duration (SD), efficacy and safety. RESULTS: 46 patients treated for a major depressive episode, indicated for ECT, were recruited to this study. A significantly lower seizure threshold was observed in the experimental group during ECT titration, on average a decrease by 34.55%, from 34.23 mC to 22.4 mC, p < 0.001 (Wilcox test). We had not observed a significant effect of TMS stimulation before ECT on seizure duration or clinical outcome. Another potentially important observation of this study is that 4 patients in the experimental group developed transient symptoms of hypomania/mania, all of which were stabilized after the combined stimulation protocol was halted spontaneously within a week, without the need to administer mood stabilizers. CONCLUSION: It is likely that HF rTMS stimulation prior to ECT is a novel and simple way of reducing the ST, which is useful in certain groups of patients undergoing this important treatment modality.

• MeSH
• antikonvulziva terapeutické užití   MeSH
• depresivní porucha unipolární diagnóza   patofyziologie   terapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• elektrokonvulzívní terapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• neparametrická statistika MeSH
• transkraniální magnetická stimulace metody   MeSH
• záchvaty diagnóza   etiologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Bacteria Borrelia burgdorferi s. l. and even more the protist Toxoplasma gondii Nicolle et Manceaux, 1908, are known to affect the behaviour and mental health of their animal and human hosts. Both pathogens infect a significant fraction of human population, both are neurotropic and survive in the host's body for a long time. While latent infections were thought to be clinically asymptomatic, recent studies suggest otherwise, revealing adverse effects on human health. It was hypothesised that the specific behavioural effects of these pathogens may be side effects of general health impairments in infected individuals. This hypothesis was tested using about one hour-long survey consisting of questionnaires and performance tests on a cohort of 7,762 members of the internet population. Results showed that individuals infected with T. gondii reported worse physical and mental health, and those infected with Borrelia spp. reported worse physical health than uninfected controls. Furthermore, infected and noninfected individuals differed in several personality traits, including conscientiousness, pathogen disgust, injury disgust, Machiavellianism, narcissism, tribalism, anti-authoritarianism, intelligence, reaction time, and precision. While the majority of behavioural effects associated with Borrelia infection were similar to those associated with Toxoplasma infection, some differences were observed, such as performance in the Stroop test. Path analyses and nonparametric partial Kendall correlation tests showed that these effects were not mediated by impaired health in infected individuals, contradicting the side effects hypothesis.

• MeSH
• Borrelia * MeSH
• infekce bakteriemi rodu Borrelia * komplikace   MeSH
• kognice MeSH
• lidé MeSH
• osobnost MeSH
• Toxoplasma * MeSH
• toxoplazmóza * komplikace   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• chování nemocného fyziologie   MeSH
• psychomotorický výkon MeSH
• toxoplazmóza zvířat patofyziologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Psychopatie je pojem s dlouhou tradicí. Současný čtyřfaktorový model popisuje psychopatii v proměnných, týkajících se - interpersonálních vztahů, - afektivity, - životního stylu, a - antisociálních rysů chování. Strukturální ani funkční neuronální povaha psychopatie není plně objasněna. Patofyziologický podklad psychopatie popisuje hypotéza somatických markerů a teorie mechanismu inhibice násilného chování. Psychopatii koreluje dysfunkce systému prefrontální kůra – temporální kůra – limbický systém.

The concept of psychopathy has a long tradition. The contemporary four-factor model describes psychopathy in – interpersonal, – affective, – lifestyle, and – antisocial variables. The structural and functional neuronal basis of psychopathy has not been fully elucidated. There are two pathophysiological theories of psychopathy: somatic marker hypothesis and violence inhibition mechanism theory. Psychopathy is associated with dysfunction of the prefrontal-temporal-limbic system circuit.

• Klíčová slova
• psychopatie, čtyřfaktorový model, prefrontální, temporální, limbický obvod,
• MeSH
• asociální osobnost diagnóza   patofyziologie   psychologie   MeSH
• lidé MeSH
• limbický systém patofyziologie   MeSH
• machiavellismus MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozková kůra patofyziologie   zranění   MeSH
• nemoci mozku diagnóza   patofyziologie   psychologie   MeSH
• poranění mozku MeSH
• poruchy chování u dětí MeSH
• poruchy osobnosti MeSH
• psychologické modely MeSH
• psychopatologie MeSH
• teoretické modely MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• úvodní články MeSH

• MeSH
• idiopatické střevní záněty MeSH
• klinické lékařství MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• gastroenterologie

• MeSH
• ekonomika MeSH
• politika MeSH

• Konspekt
• Ekonomie
• NLK Obory
• ekonomie, ekonomika, ekonomika zdravotnictví

Embryonic stem cells (ESCs) proliferate rapidly and have a unique cell-cycle structure with a very short G1 phase. Previous reports suggested that the rapid G1 phase progression of ESCs might be underpinned by high and precocious Cdk2 activity and that Cdk2 activity might be crucial for both cell-cycle regulation and cell-fate decisions in human ESCs. However, the actual role of Cdk2 in cell-cycle progression of mouse ESCs (mESCs) has not been elucidated. In this study, we investigated the effects of down-regulation of Cdk2 activity by olomoucine II in 2 mESC lines. Olomoucine II treatment significantly increased the G1 phase cell numbers, decreased the S phase cell numbers, and inhibited DNA replication in mESCs. In nocodazole-synchronized mESCs, we show that specific down-regulation of Cdk2 activity prolongs G1 phase progression. In addition, down-regulation of Cdk2 activity in mESCs established a somatic cell-like cell cycle and induced expression of differentiation markers. Our results suggest that high Cdk2 activity is essential for rapid G1 phase progression and establishment of ESC-specific cell-cycle structure in mESCs and support the hypothesis of a link between cell-cycle regulation and pluripotency maintenance in ESCs. This study reveals olomoucine II to be an effective tool for manipulation of the cell cycle and pluripotency in ESCs and very likely also for the manipulation of other stem cell types, including cancer stem cells.

• MeSH
• buněčné linie MeSH
• buněčný cyklus účinky léků   MeSH
• buňky HT-29 MeSH
• časové faktory MeSH
• cyklin-dependentní kinasa 2 antagonisté a inhibitory   genetika   metabolismus   MeSH
• cyklin-dependentní kinasa 9 antagonisté a inhibitory   genetika   metabolismus   MeSH
• embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• G1 fáze účinky léků   MeSH
• inbrední kmeny myší MeSH
• inhibiční koncentrace 50 MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteinkinasa CDC2 antagonisté a inhibitory   genetika   metabolismus   MeSH
• průtoková cytometrie MeSH
• puriny farmakologie   MeSH
• replikace DNA účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The sex ratio may be influenced by many factors, such as stress and immunosuppression, age of parents, parity and sex of preceding siblings. In animal systems, parasitism often changes the sex ratio of infected hosts, which can increase the probability of their transmission. The most common human protozoan parasite in developed countries, Toxoplasma gondii (prevalence 20%-80%), is known to change the behaviour of its intermediate hosts, thereby increasing the probability of transmission to its definitive host (the cat) by predation. The intermediate hosts, which under natural conditions are rodents, serve as the vector for Toxoplasma. Therefore, we speculate that Toxoplasma can alter the secondary sex ratio (i.e. male to female ratio in the offspring) of infected females to increase the proportion of (congenitally infected) male offspring, which are the more migratory sex in most rodent species. Here we studied the sex ratio of experimentally infected laboratory mice, expressed here as the proportion of males in the litter. In accordance with our hypothesis and results of previous retrospective cohort studies on human subjects, mice with toxoplasmosis produced a higher sex ratio than controls, in the early phase of latent infection. In the later phase of infection, mice with congenital toxoplasmosis had a lower sex ratio than controls, which is in accord with the Trivers-Willard hypothesis of sex ratio manipulation, suggesting that females in poor physical condition give birth to more female offspring.

• MeSH
• časové faktory MeSH
• financování organizované MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• poměr pohlaví MeSH
• těhotenství MeSH
• Toxoplasma fyziologie   MeSH
• toxoplazmóza zvířat patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH