Gestational diabetes mellitus and peripartum depression: a longitudinal study of a bidirectional relationship.

Background: Gestational diabetes mellitus (GDM) and peripartum depression (PPD) are increasing global health issues with potentially long-lasting adverse outcomes. While limited studies suggest a bidirectional relationship between GDM and PPD, most research has been cross-sectional and focused on one direction of the relationship, primarily if GDM predicts postpartum depression. The interplay between antenatal depression and GDM is less explored, with a critical lack of prospective bidirectional studies.

Prospective study of individual characteristics and posttraumatic stress disorder (PTSD) symptoms following childbirth: Birth satisfaction as a moderator.

Objective: The goal of this study was to (a) examine the association between childbirth-related posttraumatic stress disorder (CB-PTSD) symptoms and possible risk factors of previous trauma, individual characteristics (neuroticism, anxiety sensitivity, and resilience), type of birth, and birth satisfaction and (b) explore whether birth satisfaction moderates any association between individual characteristics and CB-PTSD symptoms.

Method: This was a longitudinal questionnaire study during pregnancy and postpartum. Pregnant women ( = 396) were recruited from antenatal clinics and completed questionnaires during mid-late pregnancy (Time 1) and 6-12 weeks after childbirth (Time 2).

Mode of birth and DNA methylation at birth, in childhood, and in adolescence: Uncovering the relationship using ALSPAC data.

Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal birth compared with elective or emergency cesarean section) affects DNAm at birth, in childhood, and adolescence and whether these effects are modified by the postnatal care environment, specifically by breastfeeding and mother-infant bonding.

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence.

Background: Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects.

Flavonols as a Potential Pharmacological Intervention for Alleviating Cognitive Decline in Diabetes: Evidence from Preclinical Studies.

Diabetes mellitus is a complex metabolic disease associated with reduced synaptic plasticity, atrophy of the hippocampus, and cognitive decline. Cognitive impairment results from several pathological mechanisms, including increased levels of advanced glycation end products (AGEs) and their receptors, prolonged oxidative stress and impaired activity of endogenous mechanisms of antioxidant defense, neuroinflammation driven by the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), decreased expression of brain-derived neurotrophic factor (BDNF), and disturbance of signaling pathways involved in neuronal survival and cognitive functioning. There is increasing evidence that dietary interventions can reduce the risk of various diabetic complications.

Glucose, Insulin and Oxygen Modulate Expression of Serotonin-Regulating Genes in Human First-Trimester Trophoblast Cell Line ACH-3P.

Serotonin signaling plays an important role in regulating development and functions of the placenta. We hypothesized that metabolic disturbances associated with maternal obesity and/or gestational diabetes mellitus (GDM) affect placental serotonin homeostasis. Therefore, we examined the effects of high glucose (25 mM) and insulin (10 nM)-two hallmarks of maternal obesity and GDM-on mRNA expression of key regulators of serotonin homeostasis, including serotonin transporter (), tryptophan hydroxylase 1 (), and monoamine oxidase A (), in the first-trimester trophoblast cell line ACH-3P, focusing on oxygen levels characteristic of early human placental development.

Association of Functional Polymorphism in Gene with Alcohol Dependence and Personality Traits: Study in Cloninger's Type I and Type II Alcohol-Dependent Inpatients.

Alcohol dependence (AD) is a complex disorder with a poorly understood etiology. In this study, we investigated the relationship between genetic variation in the gene, which encodes the enzyme responsible for serotonin synthesis in the brain, and both AD and personality traits, with attention to Cloninger's types of AD. The study included 373 healthy control subjects, 206 inpatients with type I AD, and 110 inpatients with type II AD.

Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone.

Maintaining energy balance is a complex physiological function whose dysregulation can lead to obesity and associated metabolic disorders. The bioamine serotonin (5HT) is an important regulator of energy homeostasis, with its central and peripheral pools influencing energy status in opposing ways. Using sublines of rats with constitutionally increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, we have previously shown that under standard diet constitutionally higher 5HT activity is associated with increased body weight, adiposity, and impaired glucose homeostasis.

Serotonin system in the human placenta - the knowns and unknowns.

The biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT) is a chemical messenger widely distributed in the brain and various other organs. Its homeostasis is maintained by the coordinated activity of a variety of proteins, including enzymes of serotonin metabolism, transmembrane transporters of serotonin, and serotonin receptors. The serotonin system has been identified also in the placenta in rodent models as a key component of placental physiology.

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene () in the Human Placenta.

The serotonin receptor 2A gene () is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of in the placenta.

Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications for the treatment of mood disorders. Yet, individual response to SSRIs is highly variable, with only a portion of patients showing the desired therapeutic effect. To better understand the molecular basis underlying individual variability in response to SSRIs, here we comparatively studied behavioral and molecular consequences of chronic treatment with fluoxetine, a widely used SSRI, in two sublines of rats with constitutionally different serotonin (5HT) homeostasis: the high-5HT and low-5HT sublines.

Metabolic Disturbances in Rat Sublines with Constitutionally Altered Serotonin Homeostasis.

Central and peripheral serotonin (5HT) have opposing functions in the regulation of energy homeostasis. Both increasing 5HT signaling in the brain and decreasing 5HT signaling in the periphery have been proposed as potential treatments for obesity. This study investigates the relationship between constitutionally high or low 5HT activity and systemic net energy balance.

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis.

Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert opposite effects on the body weight regulation: increase in brain 5HT activity is expected to decrease body weight, whereas increase in peripheral 5HT activity will increase body weight and adiposity. In a genetic model of rats with constitutionally high- or low-5HT homeostasis (hyperserotonergic/hyposerotonergic rats), we have studied how individual differences in endogenous 5HT tone modulate net energy balance of the organism. The high-5HT and low-5HT sublines of the model were developed by selective breeding toward extreme platelet activities of 5HT transporter, a key molecule determining 5HT bioavailability/activity.

Regulatory effects of simvastatin and apoJ on APP processing and amyloid-β clearance in blood-brain barrier endothelial cells.

Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer's disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD.

Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus.

We tested the hypothesis that gestational diabetes mellitus (GDM) alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4), and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT).

DNA Methylation Analysis of HTR2A Regulatory Region in Leukocytes of Autistic Subjects.

Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated.

FTIR spectroscopy reveals lipid droplets in drug resistant laryngeal carcinoma cells through detection of increased ester vibrational bands intensity.

The major obstacle to successful chemotherapy of cancer patients is drug resistance. Previously we explored the molecular mechanisms of curcumin cross-resistance in carboplatin resistant human laryngeal carcinoma 7T cells. Following curcumin treatment we found a reduction in curcumin accumulation, and reduced induction of reactive oxygen species (ROS) and their downstream effects, compared to parental HEp-2 cells.

Phospholipid transfer protein is expressed in cerebrovascular endothelial cells and involved in high density lipoprotein biogenesis and remodeling at the blood-brain barrier.

Phospholipid transfer protein (PLTP) is a key protein involved in biogenesis and remodeling of plasma HDL. Several neuroprotective properties have been ascribed to HDL. We reported earlier that liver X receptor (LXR) activation promotes cellular cholesterol efflux and formation of HDL-like particles in an established in vitro model of the blood-brain barrier (BBB) consisting of primary porcine brain capillary endothelial cells (pBCEC).

Pharmacological activation of LXRs decreases amyloid-β levels in Niemann-Pick type C model cells.

Niemann-Pick type C disease (NPC) is an inherited disorder mainly caused by loss-of-function mutations in the NPC1 gene, that lead to intracellular cholesterol accumulation and disturbed cholesterol homeostasis. Similarly to Alzheimer's disease (AD), NPC is associated with progressive neurodegeneration and altered metabolism of amyloid precursor protein (APP). Liver X receptors (LXRs), the key transcriptional regulators of cholesterol homeostasis, were reported to play neuroprotective roles in NPC mice.

Combination of polymorphic variants in serotonin transporter and monoamine oxidase-A genes may influence the risk for early-onset alcoholism.

The combinatory effect of polymorphisms in serotonin transporter and monoamine oxidase-A genes on the aetiopathogenesis of alcoholism was investigated in a sample of 714 individuals. Increased frequency of subjects having three 'suspected' genotypes (5-HTTLPR-LL, STin2-1010 and MAO-A 3-repeat allele) was found among type-2 alcoholic patients (P=0.0189).

Association of MTHFR, MTR, MTRR, RFC1, and DHFR gene polymorphisms with susceptibility to sporadic colon cancer.

Altered folate levels may play an important role in colon carcinogenesis. The aim of this study was to investigate the association of polymorphisms in key folate-metabolizing genes with susceptibility to sporadic colon cancer. Six common polymorphisms (two in MTHFR and one each in MTR, MTRR, RFC1, and DHFR genes) were genotyped in 300 healthy subjects and 300 colon cancer patients from Croatia.