Selective reduction in the expression of type-1 metabotropic glutamate receptors in the hippocampus of adult rats born by caesarean section

Perinatal hypoxia causes long-term neurobiological consequences, including alterations in mechanisms of activity-dependent synaptic plasticity and cognitive dysfunction. Changes in neurotransmitter receptors have been associated with these alterations, but little is known on how early hypoxia influences the expression and function of metabotropic glutamate (mGlu) receptors in adult life. This is an important issue because mGlu receptors are implicated in mechanisms of synaptic plasticity. Here, we examined the expression of mGlu1, mGlu5, and mGlu2/3 receptor subtypes in the hippocampus, nucleus accumbens, prefrontal cortex, and dorsal striatum in 6-month old Wistar rats (a) born by vaginal delivery; (b) born by caesarean section; and (c) born by caesarean section followed by 20 min of asphyxia. Unexpectedly, we found a large reduction of mGlu1α protein levels in the hippocampus of rats born by caesarean section regardless of the presence of asphyxia. No changes in mGlu1α receptor protein levels were found in the other brain regions. Levels of mGlu5 and mGlu2/3 receptors and levels of GluA2/3 and GluN1 subunits of AMPA and NMDA receptors did not differ among the three groups of rats in any brain region. These results are consistent with previous findings showing that changes in mGlu1 receptors occur within the epigenetic programming caused by early-life events

Maternal stress during pregnancy and neurodevelopmental outcomes of children during the first 2 years of life

AIM: A growing body of literature documents associations between maternal stress in pregnancy and child development, but findings across studies are often inconsistent. The aim of this study was to estimate the association between exposure to different kinds of prenatal stress and child psychomotor development. METHODS: The study population consisted of 372 mother-child pairs from Polish Mother and Child Cohort. The analysis was restricted to the women who worked at least 1 month during pregnancy period. Maternal psychological stress during pregnancy was assessed based on: the Subjective Work Characteristics Questionnaire, Perceived Stress Scale and Social Readjustment Rating Scale. The level of satisfaction with family functioning and support was evaluated by APGAR Family Scale. Child psychomotor development was assessed at the 12th and 24th months of age by Bayley Scales of Infant and Toddler Development. RESULTS: Negative impact on child cognitive development at the age of two was observed for the Perceived Stress Scale (β = -0.8; P = 0.01) and the Social Readjustment Rating Scale (β = -0.4; P = 0.03) after adjusting for the variety of confounders. Occupational stress, as well as satisfaction with family functioning, was not significantly associated with child psychomotor development (P > 0.05). CONCLUSIONS: The study supports the findings that prenatal exposure to maternal stress is significantly associated with decreased child cognitive functions. In order to further understand and quantify the effects of prenatal stress on child neurodevelopment further studies are needed. This will be important for developing interventions that provide more assistance to pregnant women, including emotional support or help to manage psychological stress

Environmental Tobacco Smoke Exposure during Pregnancy and Child Neurodevelopment

The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level <10 ng/mL). Maternal passive smoking was assessed based on the cotinine level in saliva analyzed by the use of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS) and by questionnaire data. The cotinine cut-off value for passive smoking was established at 1.5 ng/mL (sensitivity 63%, specificity 71%). Psychomotor development was assessed in children at the age of one- and two-years using the Bayley Scales of Infant and Toddler Development. Approximately 30% of the women were exposed to ETS during pregnancy. The multivariate linear regression model indicated that ETS exposure in the 1st and the 2nd trimesters of pregnancy were associated with decreasing child language functions at the age of one (β = -3.0, p = 0.03, and β = -4.1, p = 0.008, respectively), and two years (β = -3.8, p = 0.05, and β = -6.3, p = 0.005, respectively). A negative association was found for cotinine level ≥1.5 ng/mL in the 2nd trimester of pregnancy and child cognition at the age of 2 (β = -4.6, p = 0.05), as well as cotinine levels ≥1.5 ng/mL in all trimesters of pregnancy and child motor abilities at two years of age (β = -3.9, p = 0.06, β = -5.3, p = 0.02, and β = -4.2, p = 0.05, for the 1st, the 2nd, and the 3rd trimester of pregnancy, respectively; for the 1st trimester the effect was of borderline statistical significance). This study confirmed that ETS exposure during pregnancy can have a negative impact on child psychomotor development within the first two years of life and underscore the importance of public health interventions aiming at reducing this exposure

Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium

Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54μg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (β=0.18, p=0.03 and β=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (β=-12.07, p=0.003 and β=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (β=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects

COVID-19 Vaccine Hesitancy in Italy: Predictors of Acceptance, Fence Sitting and Refusal of the COVID-19 Vaccination

Background: The hesitancy in taking the COVID-19 vaccine is a global challenge. The need to identify predictors of COVID-19 vaccine reluctance is critical. Our objectives were to evaluate sociodemographic, psychological, and behavioral factors, as well as attitudes and beliefs that influence COVID-19 vaccination hesitancy in the general population of Italy. Methods: A total of 2,015 people were assessed in two waves (March, April and May, 2021). Participants were divided into three groups: (1) individuals who accepted the vaccination (“accepters”); (2) individuals who refused the vaccination (“rejecters”); and (3) individuals who were uncertain about their attitudes toward the vaccination (“fence sitters”). Group comparisons were performed using ANOVA, the Kruskal-Wallis test and chi-square tests. The strength of the association between the groups and the participants' characteristics was analyzed using a series of multinomial logistic regression models with bootstrap internal validation (one for each factor). Results: The “fence sitters” group, when compared to the others, included individuals of younger age, lower educational level, and worsening economic situation in the previous 3 months. After controlling for sociodemographic factors, the following features emerged as the main risk factors for being “fence sitters” (compared with vaccine “accepters”): reporting lower levels of protective behaviors, trust in institutions and informational sources, frequency of use of informational sources, agreement with restrictions and higher conspirative mentality. Higher levels of COVID-19 perceived risk, trust in institutions and informational sources, frequency of use of informational sources, agreement with restrictions and protective behaviors were associated with a higher likelihood of becoming “fence sitters” rather than vaccine “rejecters.” Conclusions: The “fence sitters” profile revealed by this study is intriguing and should be the focus of public programmes aimed at improving adherence to the COVID-19 vaccination campaign

Sex-dependent effects of developmental lead exposure in Wistar rats: Evidence from behavioral and molecular correlates

Lead (Pb) exposure in early life affects brain development resulting in cognitive and behavioral deficits. Epidemiologic and experimental evidence of sex as an effect modifier of developmental Pb exposure is emerging. In the present study, we investigated Pb effects on behavior and mechanisms of neuroplasticity in the hippocampus and potential sex differences. To this aim, dams were exposed, from one month pre-mating to offspring weaning, to Pb via drinking water at 5 mg/kg body weight per day. In the offspring of both sexes, the longitudinal assessment of motor, emotional, and cognitive end points was performed. We also evaluated the expression and synaptic distribution of N-methyl-D-Aspartate receptor (NMDA) and ff-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits at post-natal day (pnd) 23 and 70 in the hippocampus. Neonatal motor patterns and explorative behavior in offspring were affected in both sexes. Pb effects in emotional response and memory retention were observed in adult females only, preceded by increased levels of GluN2A and GluA1 subunits at the post-synapse at pnd 23. These data suggest that Pb exposure during development affects glutamatergic receptors distribution at the post-synaptic spine in females. These effects may contribute to alterations in selected behavioral domains

Gestational diabesity and foetoplacental vascular dysfunction

Gestational diabetes mellitus (GDM) shows a deficiency in the metabolism of D-glucose and other nutrients, thereby negatively affecting the foetoplacental vascular endothelium. Maternal hyperglycaemia and hyperinsulinemia play an important role in the aetiology of GDM. A combination of these and other factors predisposes women to developing GDM with pre-pregnancy normal weight, viz. classic GDM. However, women with GDM and prepregnancy obesity (gestational diabesity, GDty) or overweight (GDMow) show a different metabolic status than women with classic GDM. GDty and GDMow are associated with altered l-arginine/nitric oxide and insulin/adenosine axis signalling in the human foetoplacental microvascular and macrovascular endothelium. These alterations differ from those observed in classic GDM. Here, we have reviewed the consequences of GDty and GDMow in the modulation of foetoplacental endothelial cell function, highlighting studies describing the modulation of intracellular pH homeostasis and the potential implications of NO generation and adenosine signalling in GDty-associated foetal vascular insulin resistance. Moreover, with an increase in the rate of obesity in women of childbearing age worldwide, the prevalence of GDty is expected to increase in the next decades. Therefore, we emphasize that women with GDty and GDMow should be characterized with a different metabolic state from that of women with classic GDM to develop a more specific therapeutic approach for protecting the mother and foetus

Thyroid hormone metabolism and environmental chemical exposure

<p>Abstract</p> <p>Background</p> <p>Polychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism.</p> <p>Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort.</p> <p>Methods</p> <p>Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels.</p> <p>Results</p> <p>The current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group.</p> <p>Conclusion</p> <p>Once again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones.</p