Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less clear and any potential safe level of alcohol use during pregnancy is not known. We evaluated the effects of prenatal alcohol on reward-related behavior and substance use in young adulthood and the potential sex differences therein. Participants were members of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort who participated in its neuroimaging follow-up in young adulthood. A total of 191 participants (28-30 years; 51% men) had complete data on prenatal exposure to alcohol, current substance use, and fMRI data from young adulthood. Maternal alcohol drinking was assessed during mid-pregnancy and pre-conception. Brain response to reward anticipation and reward feedback was measured using the Monetary Incentive Delay task and substance use in young adulthood was assessed using a self-report questionnaire. We showed that even a moderate exposure to alcohol in mid-pregnancy but not pre-conception was associated with robust effects on brain response to reward feedback (six frontal, one parietal, one temporal, and one occipital cluster) and with greater cannabis use in both men and women 30 years later. Moreover, mid-pregnancy but not pre-conception exposure to alcohol was associated with greater cannabis use in young adulthood and these effects were independent of maternal education and maternal depression during pregnancy. Further, the extent of cannabis use in the late 20 s was predicted by the brain response to reward feedback in three out of the nine prenatal alcohol-related clusters and these effects were independent of current alcohol use. Sex differences in the brain response to reward outcome emerged only during the no loss vs. loss contrast. Young adult men exposed to alcohol prenatally had significantly larger brain response to no loss vs. loss in the putamen and occipital region than women exposed to prenatal alcohol. Therefore, we conclude that even moderate exposure to alcohol prenatally has long-lasting effects on brain function during reward processing and risk of cannabis use in young adulthood.

• MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie * MeSH
• mozek * diagnostické zobrazování   účinky léků   patofyziologie   MeSH
• odměna * MeSH
• pití alkoholu * psychologie   škodlivé účinky   MeSH
• sexuální faktory MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví 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

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

• MeSH
• dospělí MeSH
• hypoxie plodu komplikace   patofyziologie   MeSH
• ischemická choroba srdeční epidemiologie   etiologie   patofyziologie   MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• reperfuzní poškození myokardu epidemiologie   etiologie   patofyziologie   MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• srdce embryologie   patofyziologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice epidemiologie   etiologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Maternal stress during pregnancy and shortly thereafter is associated with altered offspring brain development that may increase risk of mood and anxiety disorders. Cortical gyrification is established during the prenatal period and the first 2 years of life and is altered in psychiatric disorders. Here, we sought to characterize the effects of perinatal stress exposure on offspring gyrification patterns and mood dysregulation in young adulthood. Participants included 85 young adults (56.5% women; 23-24 years) from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with perinatal stress data across four distinct timepoints and structural MRI data from young adulthood. Perinatal stress exposure was measured as maternal stress during first and second half of pregnancy, first 6 months, and 6-18 months after birth. Cortical gyrification and mood dysregulation were quantified using local gyrification index (LGI), computed with Freesurfer, and the Profile of Mood States questionnaire, respectively. Perinatal stress predicted cortical gyrification in young adulthood, and its timing influenced location, direction, and sex-specificity of effects. In particular, whereas early prenatal stress was associated with sex-dependent medium-to-large effects in large temporal, parietal, and occipital regions (f2 = 0.19-0.38, p < .001), later perinatal stress was associated with sex-independent small-to-medium effects in smaller, more anterior regions (f2 = 0.10-0.19, p < .003). Moreover, in females, early prenatal stress predicted higher LGI in a large temporal region, which was further associated with mood disturbance in adulthood (r = 0.399, p = .006). These findings point out the long-term implications of perinatal stress exposure for cortical morphology and mood dysregulation.

• MeSH
• afektivní symptomy * diagnostické zobrazování   etiologie   patologie   patofyziologie   MeSH
• dospělí MeSH
• emoční regulace fyziologie   MeSH
• kojenec MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• mozková kůra * diagnostické zobrazování   patologie   patofyziologie   MeSH
• novorozenec MeSH
• poporodní období MeSH
• psychický stres komplikace   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * diagnostické zobrazování   etiologie   patologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The placenta is the first organ to be created during mammalian development. As the main link between the mother and the fetus it has more diverse functions than any other organ, serving as a digestive, excretory, respiratory, endocrine, and immune system. The outer layer of the placenta, the trophoblast, plays a key role in fetal development by orchestrating all these functions. Recent research has associated perturbations of maternal conditions (such as malnutrition, stress or inflammation) with alterations of the trophoblasts' endocrine, transport and metabolic processes. As reviewed here, adaptations to these conditions enable the fetus to survive, but at the cost of permanently changing its physiology and structure. Moreover, these adaptations trigger fetal programming that increases predisposition to various pathological conditions in adult life, typically metabolic, cardiovascular or CNS diseases.

• MeSH
• biologické modely MeSH
• lidé MeSH
• maternofetální výměna látek účinky léků   fyziologie   MeSH
• placenta fyziologie   MeSH
• těhotenství MeSH
• trofoblasty cytologie   účinky léků   fyziologie   MeSH
• vývoj plodu účinky léků   fyziologie   MeSH
• xenobiotika toxicita   MeSH
• zpožděný efekt prenatální expozice etiologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Modafinil is a psychostimulant drug prescribed for treatment of narcolepsy. However, it is used as a "smart drug" especially by young adults to increase wakefulness, concentration and mental performance. Therefore, it can also be used by women with childbearing potential and its developmental effects can become a concern. The aim of this study was to assess behavioural and immune effects of prenatal modafinil exposure in mice and to evaluate the reaction to methamphetamine exposure on these animals in adult age. Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestation day (GD) 3 to GD 10 and then a challenge dose on GD 17. The male offspring were treated analogously at the age of 10 weeks with methamphetamine (2.5 mg/kg orally). Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open field test were assessed in naïve animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. The modafinil prenatally exposed mice showed basal hypolocomotion, increased anxiety, lower locomotor effect of acute methamphetamine and increased vulnerability to behavioural sensitization. The leukocyte activity did not show significant differences. Prenatal modafinil exposure alters basal behavioural profile, decreases acute effect of methamphetamine and enhances vulnerability to development of behavioural sensitization at adulthood. This may lead to higher vulnerability to development of addiction.

• MeSH
• analýza rozptylu MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• fagocytóza účinky léků   MeSH
• gestační stáří MeSH
• leukocyty účinky léků   MeSH
• lokomoce účinky léků   MeSH
• methamfetamin farmakologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• novorozená zvířata MeSH
• pátrací chování účinky léků   MeSH
• pohybová aktivita účinky léků   MeSH
• stimulancia toxicita   MeSH
• stimulanty centrálního nervového systému farmakologie   MeSH
• těhotenství MeSH
• věkové faktory MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.

• MeSH
• krysa rodu rattus MeSH
• maternální deprivace MeSH
• mateřské chování účinky léků   fyziologie   psychologie   MeSH
• methamfetamin toxicita   MeSH
• metoda rotující tyčky metody   psychologie   MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• poruchy spojené s užíváním psychoaktivních látek komplikace   patofyziologie   psychologie   MeSH
• potkani Wistar MeSH
• psychický stres komplikace   patofyziologie   psychologie   MeSH
• psychomotorický výkon účinky léků   fyziologie   MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH). A period of 20 days was allowed for the development of the depressive-like phenotype. Animals were tested in the motor activity test and 2 % sucrose preference for anhedonia and hyperactive locomotor response to a novel environment, respectively. After then females were impregnated. Pregnant females were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline (SA) during the entire gestation period. Postnatally, maternal behavior and pup development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on behavior was further examined in adult male offspring. Our results showed no differences in the maternal behavior as a matter of bulbectomy, only OBX rats slept more than all the SH controls. Pups from OBX mothers were born with lower birthweight and gained less weight during the postnatal development than pups from SH controls. Both, bulbectomy and MA administration, delayed the eyes opening. As a matter of functional development of the pups, maternal OBX procedure impaired the performance in the Bar-holding test, but only in saline group. OBX/SA group was the worst in the Bar-holding test relative to all the other groups. In addition, pups from OBX mothers dropped more boluses during the Bar-holding test, suggesting that they were more stressed. In adult male offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA exposure increased locomotion, while decreasing immobility. In addition, challenge dose of MA in adulthood increased distance traveled, locomotion, rearing, and average and maximal velocity, while decreasing immobility and grooming. In conclusion, our results suggest that depressive-like phenotype of rat mothers induces impairment in somatic and functional development of their male offspring.

• MeSH
• bulbus olfactorius chirurgie   MeSH
• krysa rodu rattus MeSH
• lokomoce MeSH
• methamfetamin toxicita   MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   fyziologie   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In modern societies, living organisms are exposed daily to multiform pollution from industrial chemical products. Some of these substances have been shown to affect the endocrine system, and have been termed endocrine disruptors (EDs). Bisphenol A (BPA), which can leach from plastics, and parabens, used in cosmetic products, are among the most well-studied. Prenatal development is a vulnerable phase of human life, and disruptions during this period may have lifelong consequences. Since EDs are known to cross the placental barrier and BPA may accumulate in the fetus, "BPA-free" products have been introduced to the market. However, such products often contain alternative bisphenols (e.g. BPS, BPF) that have not yet been extensively examined or regulated. Moreover, alternative bisphenols often occur together with BPA. The human organism is thus exposed to a mixture of EDs, some of which can have additive or synergic effects. Recent findings have also shown that paraben exposure can alter bisphenol pharmacokinetics. Taking into account the widespread occurrence of various EDs and the potential multiplicity of their effects, doses of EDs currently considered safe may not actually be as safe as they appear, especially during pregnancy.

• MeSH
• benzhydrylové sloučeniny škodlivé účinky   metabolismus   MeSH
• endokrinní disruptory škodlivé účinky   metabolismus   MeSH
• fenoly škodlivé účinky   metabolismus   MeSH
• lidé MeSH
• parabeny škodlivé účinky   metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the drugs.

• MeSH
• analgetika farmakologie   MeSH
• analýza rozptylu MeSH
• bludiště - učení účinky léků   MeSH
• časové faktory MeSH
• estrální cyklus účinky léků   MeSH
• krysa rodu rattus MeSH
• methamfetamin toxicita   MeSH
• N-methyl-3,4-methylendioxyamfetamin farmakologie   MeSH
• pátrací chování účinky léků   MeSH
• serotoninové látky farmakologie   MeSH
• sexuální faktory MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• úzkost chemicky indukované   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH