The interaction between the main psychotropic ingredient of Cannabis, Δ9- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis. Sprague Dawley dams were exposed to THC (2 mg/kg) or vehicle, from gestational day 5-20. The adolescent progeny of both sexes was tested for: spatial memory retrieval and flexibility in the Barnes Maze; mRNA expression of relevant players of hippocampal synaptic plasticity; density of cholecystokinin-positive basket cells (CCK+BCs) - a major subtype of hippocampal inhibitory interneurons; mRNA expression of the excitatory and inhibitory synaptic proteins neuroligins (Nlgns), as a proxy of synaptic efficiency. Our results show a sex-specific disruption in spatial memory retrieval and flexibility, a male-specific decrease in CCK+BCs density and increase in the expression of markers of neuroplasticity, and consistent changes in the expression of Nlgn-1 and 3 isoforms. Despite a delay in memory retrieval, flexibility of memory was spared in prenatally-THC-exposed female offspring as well as most of the markers of neuroplasticity; a sex-specific increase in CCK+BCs density, and a consistent expression of Nlgn-3 was observed. The current results highlight a major vulnerability to prenatal exposure to THC on memory processing in the male progeny, and sex-specific alterations in the E/I balance and synaptic plasticity.

• MeSH
• bludiště - učení účinky léků   MeSH
• cholecystokinin metabolismus   MeSH
• hipokampus * účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• neuroplasticita * účinky léků   MeSH
• pohlavní dimorfismus * MeSH
• potkani Sprague-Dawley * MeSH
• prostorová paměť * účinky léků   MeSH
• těhotenství MeSH
• tetrahydrokanabinol * farmakologie   toxicita   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children.

• MeSH
• dítě MeSH
• gastrointestinální látky terapeutické užití   škodlivé účinky   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• idiopatické střevní záněty * farmakoterapie   imunologie   MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• ustekinumab * terapeutické užití   škodlivé účinky   MeSH
• vakcinace * škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

INTRODUCTION: Both maternal depression problems during pregnancy and prenatal exposure to air pollution have been associated with changes in the brain as well as worse mood and anxiety in the offspring in adulthood. However, it is not clear whether these effects are independent or whether and how they might interact and impact the brain age and mental health of the young adult offspring. METHODS: A total of 202 mother-child dyads from a prenatal birth cohort were assessed for maternal depression during pregnancy through self-report questionnaires administered in the early 90s, exposure to air pollutants (Sulfur dioxide [SO2], nitrogen oxides [NOx], and suspended particle matter [SPM]) during each trimester based on maternal address and air quality data, mental health of the young adult offspring (28-30 years of age; 52% men, all of European ancestry) using self-report questionnaires for depression (Beck Depression Inventory), mood dysregulation (Profile of Mood States), anxiety (State-Trait Anxiety Inventory), and psychotic symptoms (Schizotypal Personality Questionnaire), and brain age, estimated from structural magnetic resonance imaging (MRI) and previously published neuroanatomical age prediction model using cortical thickness maps. The brain age gap estimate (BrainAGE) was computed by subtracting structural brain age from chronological age. Trajectories of exposure to air pollution during pregnancy were assessed using Growth Mixture Modeling. The interactions of prenatal depression and prenatal exposure to air pollutants on adult mental health and BrainAGE were assessed using hierarchical linear regression. RESULTS: We revealed two distinct trajectories of exposure to air pollution during pregnancy: "early exposure," characterized by high exposure during the first trimester, followed by a steady decrease, and "late exposure," characterized by low exposure during the first trimester, followed by a steady increase in the exposure during the subsequent trimesters. Maternal depression during the first half of pregnancy interacted with NOX exposure trajectory, predicting mood dysregulation and schizotypal symptoms in young adults. In addition, maternal depression during the second half of pregnancy interacted with both NOx and SO2 exposure trajectories, respectively, and predicted BrainAGE in young adults. In those with early exposure to NOx, maternal depression during pregnancy was associated with worse mental health and accelerated brain aging in young adulthood. In contrast, in those with early exposure to SO2, maternal depression during pregnancy was associated with slower brain aging in young adulthood. CONCLUSIONS: Our findings provide the first evidence of the combined effects of prenatal exposure to air pollution and maternal depression on mental health outcomes and brain age in young adult offspring. Moreover, they point out the importance of the timing and trajectory of the exposure during prenatal development.

• MeSH
• deprese * chemicky indukované   MeSH
• dospělí MeSH
• duševní zdraví MeSH
• kohortové studie MeSH
• látky znečišťující vzduch škodlivé účinky   toxicita   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * účinky léků   růst a vývoj   diagnostické zobrazování   MeSH
• stárnutí MeSH
• těhotenství MeSH
• znečištění ovzduší * škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Autism spectrum disorder (ASD) is a psychiatric disorder with severe behavioral consequences and no specific therapy. Its etiology is multifactorial, as it is caused by a complex interaction of genetic and environmental factors. In rats, prenatal exposure to the antiepileptic drug valproic acid (VPA) has been associated with an increased risk of autistic-like behaviors in offspring, including social behavior deficits, increased repetitive behaviors, and cognitive impairments. In addition, VPA-treated rats have shown altered sociosexual behaviors. However, the mechanisms underlying these alterations in reproductive processes in VPA-treated rats are not fully understood. Interestingly some abnormal behaviors in VPA autism models are improved by an enriched environment (EE). In the present study, we examined the effects of EE on memory performance and sexual behavior in male rats. We found that on postnatal day 90, EE reduced the time it took for both control and VPA-treated groups to find a hidden platform in the Morris water maze. On PND 100, prenatal exposure to VPA reduced total exploring time in object recognition tests. On PND 110, EE reduced mount and intromission latency and increased ejaculatory frequency in VPA-treated male rats. These results suggest that environmental stimuli significantly influence the onset of sexual behavior in VPA-treated male rats and that EE may be a potential tool for improving a variety of behavioral deficiencies in rodent models of autism.

• MeSH
• autistická porucha * chemicky indukované   MeSH
• krysa rodu rattus MeSH
• kyselina valproová škodlivé účinky   MeSH
• lidé MeSH
• poruchy autistického spektra * chemicky indukované   MeSH
• sexuální chování MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.

• MeSH
• akrylamid toxicita   MeSH
• apoptóza MeSH
• aromatasa * genetika   MeSH
• furylfuramid MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• poměr pohlaví MeSH
• potkani Wistar MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Maternal immune activation has been identified as a significant risk factor for schizophrenia. Using rodent models, past work has demonstrated various behavioral and brain impairments in offspring after immune-activating events. We applied 5 mg/kg of poly(I:C) on gestation day 9 to pregnant mouse dams, whose offspring were then stressed during puberty. We show impairments in attentional set-shifting in a T-maze, and a decreased number of parvalbumin-positive interneurons in the hippocampus as a result of peripubertal stress specifically in females.

• MeSH
• chování zvířat fyziologie   MeSH
• exekutivní funkce fyziologie   MeSH
• hipokampus cytologie   MeSH
• infekční komplikace v těhotenství * chemicky indukované   imunologie   MeSH
• interneurony cytologie   MeSH
• kognitivní dysfunkce etiologie   patologie   patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• poly I-C aplikace a dávkování   MeSH
• pozornost fyziologie   MeSH
• psychický stres komplikace   patologie   patofyziologie   MeSH
• schizofrenie etiologie   imunologie   patologie   patofyziologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

There is growing evidence that methamphetamine use during pregnancy may produce detrimental cardiovascular effects in the adult offspring. Prior work demonstrated that chronic methamphetamine exposure throughout the gestational period causes adult female offspring to become hypersensitive to myocardial ischemic injury. The goal of the present study was to determine whether this methamphetamine-induced effect occurs early or late in the gestational period. Pregnant female rats were divided into 4 experimental groups. Groups 1 and 2 received subcutaneous injections of saline (group 1) or methamphetamine (5 mg/kg) (group 2) throughout the gestational period. Group 3 received methamphetamine injections on days 1-11 and saline on days 12-22, and group 4 received saline on days 1-11 and methamphetamine on days 12-22. Hearts were isolated from adult (8 weeks) female offspring and subjected to 30 min ischemia and 2 hours reperfusion on a Langendorff isolated heart apparatus. Contractile function was measured via an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Infarcts were significantly larger in methamphetamine exposed offspring regardless of whether they had been exposed to methamphetamine during the first half or the second half of the gestational period. Prenatal exposure to methamphetamine had no effect on preischemic contractile function or postischemic recovery of contractile function. These data indicate that methamphetamine use during either the first half or second half of pregnancy increases susceptibility to myocardial infarction in adult female offspring. These data provide further evidence that prenatal exposure to methamphetamine may increase the risk of developing cardiovascular diseases during adulthood.

• MeSH
• infarkt myokardu * MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• methamfetamin * toxicita   MeSH
• poranění srdce * MeSH
• potkani Sprague-Dawley MeSH
• srdce MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Schizophrenia is a severe neuropsychiatric disease associated with substantially higher mortality. Reduced life expectancy in schizophrenia relates to an increased prevalence of metabolic disturbance, and antipsychotic medication is a major contributor. Molecular mechanisms underlying adverse metabolic effects of antipsychotics are not fully understood; however, adipose tissue homeostasis deregulation appears to be a critical factor. We employed mass spectrometry-based untargeted proteomics to assess the effect of chronic olanzapine, risperidone, and haloperidol treatment in visceral adipose tissue of prenatally methylazoxymethanol (MAM) acetate exposed rats, a well-validated neurodevelopmental animal model of schizophrenia. Bioinformatics analysis of differentially expressed proteins was performed to highlight the pathways affected by MAM and the antipsychotics treatment. MAM model was associated with the deregulation of the TOR (target of rapamycin) signalling pathway. Notably, alterations in protein expression triggered by antipsychotics were observed only in schizophrenia-like MAM animals where we revealed hundreds of affected proteins according to our two-fold threshold, but not in control animals. Treatments with all antipsychotics in MAM rats resulted in the downregulation of mRNA processing and splicing, while drug-specific effects included among others upregulation of insulin resistance (olanzapine), upregulation of fatty acid metabolism (risperidone), and upregulation of nucleic acid metabolism (haloperidol). Our data indicate that deregulation of several energetic and metabolic pathways in adipose tissue is associated with APs administration and is prominent in MAM schizophrenia-like model but not in control animals.

• MeSH
• antipsychotika terapeutické užití   MeSH
• haloperidol farmakologie   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• methylazoxymethanolacetát farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• nitrobřišní tuk účinky léků   embryologie   metabolismus   MeSH
• olanzapin farmakologie   terapeutické užití   MeSH
• potkani Sprague-Dawley MeSH
• proteomika MeSH
• risperidon farmakologie   terapeutické užití   MeSH
• schizofrenie farmakoterapie   MeSH
• signální transdukce účinky léků   MeSH
• těhotenství MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• tuková tkáň účinky léků   metabolismus   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.

• MeSH
• dibutylftalát toxicita   MeSH
• diethylhexylftalát toxicita   MeSH
• krysa rodu rattus MeSH
• kyseliny ftalové toxicita   MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• novorozená zvířata MeSH
• pohlavní dospělost MeSH
• pohlavní orgány účinky léků   patologie   MeSH
• potkani Wistar MeSH
• sociální chování * MeSH
• těhotenství MeSH
• testosteron krev   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patologie   MeSH
• zvířata MeSH
• zvláčňovadla toxicita   MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Di-(2-ethylhexyl)-phthalate (DEHP) is a compound widely used as a plasticizer, which can leach from plastics into the environment and thus influence human health. The aim of this study was to analyze whether exposure to an environmentally relevant dose of DEHP during mice fetal development or puberty can cause long-lasting changes detectable month/s after the last exposure. We used a DEHP concentration relevant to a daily human intake of 2.4-3 μg/kg of body weight/day. CD1 outbred mice were treated either in utero or postnatally during puberty and analyzed in adulthood. Analyzing fertility parameters using morphometric, histologic, genomic and proteomic methods we showed that DEHP exposure leads to decreased sperm concentration and quality, in both experimental groups. Moreover, the changes in anogenital distance, seminal vesicle weight, and testicular gene expression suggest a disturbance of androgen signaling in exposed animals. In conclusion, we hereby present, that the prenatal and pubertal exposure to a low dose of DEHP negatively influenced reproductive endpoints in male mice, and some of the effects were persistent until adulthood.

• MeSH
• anální kanál anatomie a histologie   účinky léků   MeSH
• diethylhexylftalát toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• maternofetální výměna látek MeSH
• mužské pohlavní orgány anatomie a histologie   účinky léků   MeSH
• myši inbrední ICR MeSH
• pohlavní dospělost účinky léků   MeSH
• spermie účinky léků   MeSH
• těhotenství MeSH
• testis anatomie a histologie   účinky léků   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   genetika   MeSH
• zvířata MeSH
• zvláčňovadla toxicita   MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH