Cancer treatment brings about a phenomenon not fully clarified yet, termed chemobrain. Its strong negative impact on patients' well-being makes it a trending topic in current research, interconnecting many disciplines from clinical oncology to neuroscience. Clinical and animal studies have often reported elevated concentrations of proinflammatory cytokines in various types of blood cancers. This inflammatory burst could be the background for chemotherapy-induced cognitive deficit in patients with blood cancers. Cancer environment is a dynamic interacting system. The review puts into close relationship the inflammatory dysbalance and oxidative/nitrosative stress with disruption of the blood-brain barrier (BBB). The BBB breakdown leads to neuroinflammation, followed by neurotoxicity and neurodegeneration. High levels of intracellular reactive oxygen species (ROS) induce the progression of cancer resulting in increased mutagenesis, conversion of protooncogenes to oncogenes, and inactivation of tumor suppression genes to trigger cancer cell growth. These cell alterations may change brain functionality, as well as morphology. Multidrug chemotherapy is not without consequences to healthy tissue and could even be toxic. Specific treatment impacts brain function and morphology, functions of the immune system, and metabolism in a unique mixture. In general, a chemo-drug's effects on cognition in cancer are not direct and/or in-direct, usually a combination of effects is more probable. Last but not least, chemotherapy strongly impacts the immune system and could contribute to BBB disruption. This review points out inflammation as a possible mechanism of brain damage during blood cancers and discusses chemotherapy-induced cognitive impairment.

• MeSH
• hematologické nádory * metabolismus   patologie   MeSH
• imunitní systém MeSH
• kognitivní porucha po chemoterapii * metabolismus   patologie   MeSH
• lidé MeSH
• mozek metabolismus   MeSH
• nádory * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The cerebellum hosts more than half of all neurons of the human brain, with their organized activity playing a key role in coordinating motor functions. Cerebellar activity has also been implicated in the control of speech, communication, and social behavior, which are compromised in autism spectrum disorders (ASD). Despite major research advances, there is a shortage of mechanistic data relating cellular and molecular changes in the cerebellum to autistic behavior. We studied the impact of tuberous sclerosis complex 2 haploinsufficiency (Tsc2+/-) with downstream mTORC1 hyperactivity on cerebellar morphology and cellular organization in 1, 9, and 18 m.o. Eker rats, to determine possible structural correlates of an autism-like behavioural phenotype in this model. We report a greater developmental expansion of the cerebellar vermis, owing to enlarged white matter and thickened molecular layer. Histochemical and immunofluorescence data suggest age-related demyelination of central tract of the vermis, as evident from reduced level of myelin-basic protein in the arbora vitae. We also observed a higher number of astrocytes in Tsc2+/- rats of older age while the number of Purkinje cells (PCs) in these animals was lower than in wild-type controls. Unlike astrocytes and PCs, Bergmann glia remained unaltered at all ages in both genotypes, while the number of microglia was higher in Tsc2+/- rats of older age. The convergent evidence for a variety of age-dependent cellular changes in the cerebellum of rats associated with mTORC1 hyperactivity, thus, predicts an array of functional impairments, which may contribute to the developmental onset of an autism-like behavioral phenotype in this model. LAY SUMMARY: This study elucidates the impact of constitutive mTORC1 hyperactivity on cerebellar morphology and cellular organization in a rat model of autism and epilepsy. It describes age-dependent degeneration of Purkinje neurons, with demyelination of central tract as well as activation of microglia, and discusses the implications of these changes for neuro-behavioral phenotypes. The described changes provide new indications for the putative mechanisms underlying cerebellar impairments with their age-related onset, which may contribute to the pathobiology of autism, epilepsy, and related disorders.

• MeSH
• autistická porucha * MeSH
• demyelinizační nemoci * komplikace   metabolismus   MeSH
• epilepsie * komplikace   MeSH
• fenotyp MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mechanistické cílové místo rapamycinového komplexu 1 genetika   metabolismus   MeSH
• mozeček metabolismus   MeSH
• poruchy autistického spektra * MeSH
• tuberózní skleróza MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1-2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 h after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.

• MeSH
• antikonvulziva farmakologie   MeSH
• epilepsie farmakoterapie   MeSH
• kanabidiol farmakokinetika   farmakologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   MeSH
• N-methylaspartát farmakologie   MeSH
• pentylentetrazol farmakologie   MeSH
• potkani Wistar MeSH
• záchvaty farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Victimization is associated with worse social and clinical outcomes of individuals with severe mental illness (SMI). A relapse of SMI may be one of the clinical consequences of assaultive trauma. As far as we know, there is no published study that analyzes nationwide health registers to assess the risk of SMI rehospitalization following assault. AIM: We aimed to assess whether exposure to assault is associated with an increased risk of psychiatric hospitalization in those with SMI. METHODS: We utilized data from the Czech nationwide registers of all-cause hospitalizations and all-cause deaths. We defined exposed individuals as those discharged from a hospitalization for SMI between 2002 and 2007, and hospitalized for serious injuries sustained in an assault in the subsequent 7 years. For each assaulted individual, we randomly selected five counterparts, matched on SMI diagnosis, age and sex, who were not assaulted in the examined time period. We used mixed effect logistic regression to assess the effect of assault on the risk of SMI rehospitalization within the following 6 months. We fitted unadjusted models and models adjusted for the number of previous SMI hospitalizations and drug use disorders. RESULTS: The sample consisted of 248 exposed and 1 240 unexposed individuals. In the unadjusted model, assaulted individuals were almost four times more likely to be rehospitalized than their non-assaulted counterparts (odds ratio (OR) = 3.96; 95% CI 2.75; 5.71). After adjusting for all covariates, the OR remained threefold higher (OR = 3.07; 95% CI 2.10; 4.49). CONCLUSION: People with a history of SMI hospitalization were approximately three times more likely to be rehospitalized for SMI within 6 months after an assault than their non-assaulted SMI counterparts. Soon after a person with SMI is physically assaulted, there should be a psychiatric evaluation and a close follow-up.

• Publikační typ
• časopisecké články MeSH

Slow-wave synchronous acoustic stimulation is a promising research and therapeutic tool. It is essential to clearly understand the principles of the synchronization methods, to know their performances and limitations, and, most importantly, to have a clear picture of the effect of stimulation on slow-wave activity (SWA). This paper covers the mentioned and currently missing parts of knowledge that are essential for the appropriate development of the method itself and future applications. Artificially streamed real sleep EEG data were used to quantitatively compare the two currently used real-time methods: the phase-locking loop (PLL) and the fixed-step stimulus in our own implementation. The fixed-step stimulation method was concluded to be more reliable and practically applicable compared to the PLL method. The sleep experiment with chronic insomnia patients in our sleep laboratory was analyzed in order to precisely characterize the effect of sound stimulation during deep sleep. We found that there is a significant phase synchronization of delta waves, which were shown to be the most sensitive metric of the effect of acoustic stimulation compared to commonly used averaged signal and power analyses. This finding may change the understanding of the effect and function of the SWA stimulation described in the literature.

• MeSH
• akustická stimulace MeSH
• elektroencefalografie MeSH
• fyzioterapie (techniky) MeSH
• lidé MeSH
• spánek pomalých vln * MeSH
• spánek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Evidence from clinical and preclinical studies implicates dysfunction of N-methyl-D-aspartate receptors (NMDARs) in schizophrenia progression and symptoms. We investigated the antipsychotic effect of two neuroactive steroids in an animal model of schizophrenia induced by systemic application of MK-801. The neuroactive steroids differ in their mechanism of action at NMDARs. MS-249 is positive, while PA-Glu is a negative allosteric NMDAR modulator. We hypothesized that the positive NMDA receptor modulator would attenuate deficits caused by MK-801 co-application more effectively than PA-Glu. The rats were tested in a battery of tests assessing spontaneous locomotion, anxiety and cognition. Contrary to our expectations, PA-Glu exhibited a superior antipsychotic effect to MS-249. The performance of MS-249-treated rats in cognitive tests differed depending on the level of stress the rats were exposed to during test sessions. In particular, with the increasing severity of stress exposure, the performance of animals worsened. Our results demonstrate that enhancement of NMDAR function may result in unspecific behavioral responses. Positive NMDAR modulation can influence other neurobiological processes besides memory formation, such as anxiety and response to stress.

• MeSH
• antipsychotika farmakologie   MeSH
• bicyklické sloučeniny heterocyklické metabolismus   MeSH
• chování zvířat účinky léků   MeSH
• dizocilpinmaleát farmakologie   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani Long-Evans MeSH
• potkani Wistar MeSH
• pregnenolon metabolismus   farmakologie   MeSH
• receptory N-methyl-D-aspartátu antagonisté a inhibitory   metabolismus   MeSH
• schizofrenie farmakoterapie   metabolismus   MeSH
• steroidy farmakologie   MeSH
• test vyvýšeného křížového bludiště MeSH
• úleková reakce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Namesaking (naming a child after a parent or other relative) can be viewed as a mechanism to increase perceived parent-child similarity and, consequently, parental investment. Male and, to a lesser extent, firstborn children are more frequently namesakes than female and later-born children, respectively. However, a direct link between namesaking and parental investment has not been examined. In the present study, 632 participants (98 men and 534 women) from Central Europe indicated their first name, sex, birth order, number of siblings, sexual orientation, socioeconomic status, paternal and maternal first names, as well as relationship quality with, and time and financial investment they received from, both parents during childhood. Mixed-effects models revealed associations between namesaking and parental investment. However, the effect of namesaking often appeared significant only in interaction with specific predictors, such as sex and primogeniture. It suggests instead that namesaking has an additive effect-it enhances the effect of biological factors on parental investment. In general, we found evidence for the bias in parental investment linked to name similarity among both parents, and support for the hypothesis that namesaking serves as a mechanism to increase paternity confidence and, thus, paternal investment. The effect of namesaking influences only certain types of parental investment-namely, those at the level of relationship quality. In addition, nonheterosexual orientation was the strongest negative predictor of paternal investment. Our study extends the research on parental investment by showing that cultural mechanisms, such as namesaking, can also exert some influence on parental rearing behavior.

• MeSH
• lidé MeSH
• otcové * MeSH
• paternita MeSH
• pořadí narození MeSH
• rodiče * MeSH
• rodinné vztahy MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.

• MeSH
• chování zvířat * MeSH
• imunohistochemie MeSH
• imunomodulace * MeSH
• interneurony metabolismus   MeSH
• krysa rodu rattus MeSH
• lipopolysacharidy imunologie   MeSH
• matka - expozice noxám MeSH
• mikroglie imunologie   metabolismus   MeSH
• mozek imunologie   metabolismus   MeSH
• parvalbuminy metabolismus   MeSH
• sexuální faktory MeSH
• sociální chování MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Research of treatment options addressing the cognitive deficit associated with neurodegenerative disorders is of particular importance. Application of trimethyltin (TMT) to rats represents a promising model replicating multiple relevant features of such disorders. N-methyl-D-aspartate (NMDA) receptor antagonists and gamma-aminobutyric acid type A (GABAA) receptor potentiators have been reported to alleviate the TMT-induced cognitive deficit. These compounds may provide synergistic interactions in other models. The aim of this study was to investigate, whether co-application of NMDA receptor antagonist dizocilpine (MK-801) and GABAA receptor potentiator midazolam would be associated with an improved effect on the TMT-induced model of cognitive deficit. Wistar rats injected with TMT were repeatedly (12 days) treated with MK-801, midazolam, or both. Subsequently, cognitive performance was assessed. Finally, after a 17-day drug-free period, hippocampal neurodegeneration (neuronal density in CA2/3 subfield in the dorsal hippocampus, dentate gyrus morphometry) were analyzed. All three protective treatments induced similar degree of therapeutic effect in Morris water maze. The results of histological analyses were suggestive of minor protective effect of the combined treatment (MK-801 and midazolam), while these compounds alone were largely ineffective at this time point. Therefore, in terms of mitigation of cognitive deficit, the combined treatment was not associated with improved effect.

• Publikační typ
• časopisecké články MeSH

Functional connectivity analysis of resting-state fMRI data has recently become one of the most common approaches to characterizing individual brain function. It has been widely suggested that the functional connectivity matrix is a useful approximate representation of the brain's connectivity, potentially providing behaviorally or clinically relevant markers. However, functional connectivity estimates are known to be detrimentally affected by various artifacts, including those due to in-scanner head motion. Moreover, as individual functional connections generally covary only very weakly with head motion estimates, motion influence is difficult to quantify robustly, and prone to be neglected in practice. Although the use of individual estimates of head motion, or group-level correlation of motion and functional connectivity has been suggested, a sufficiently sensitive measure of individual functional connectivity quality has not yet been established. We propose a new intuitive summary index, Typicality of Functional Connectivity, to capture deviations from standard brain functional connectivity patterns. In a resting-state fMRI dataset of 245 healthy subjects, this measure was significantly correlated with individual head motion metrics. The results were further robustly reproduced across atlas granularity, preprocessing options, and other datasets, including 1,081 subjects from the Human Connectome Project. In principle, Typicality of Functional Connectivity should be sensitive also to other types of artifacts, processing errors, and possibly also brain pathology, allowing extensive use in data quality screening and quantification in functional connectivity studies as well as methodological investigations.

• MeSH
• artefakty MeSH
• atlasy jako téma * MeSH
• datové soubory jako téma * MeSH
• dospělí MeSH
• hlava - pohyby MeSH
• konektom * metody   normy   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   normy   MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   fyziologie   MeSH
• počítačové zpracování obrazu * metody   normy   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH