RESUMO
The adverse effects of maternal prenatal stress (PS) on child's neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.
Assuntos
Ferritinas , Feto , Biomarcadores , Estudos de Coortes , Feminino , Sangue Fetal/metabolismo , Feto/metabolismo , Homeostase , Humanos , Recém-Nascido , Ferro/metabolismo , Masculino , Gravidez , Estudos ProspectivosRESUMO
Prenatal stress (PS) impacts early behavioral, neuroimmune, and cognitive development. Pregnant rat models have been very valuable in examining the mechanisms of such fetal programming. A newer pregnant sheep model of maternal stress offers the unique advantages of chronic in utero monitoring and manipulation. This chapter presents the techniques used to model single and multigenerational stress exposures and their pleiotropic effects on the offspring.
Assuntos
Encéfalo/patologia , Desenvolvimento Fetal/fisiologia , Doenças Fetais/patologia , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Psiconeuroimunologia/métodos , Estresse Fisiológico , Animais , Animais Recém-Nascidos , Feminino , Masculino , Gravidez , Complicações na Gravidez , Ratos , Ratos Wistar , OvinosRESUMO
Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field.