Plasma amino acids and neopterin in healthy persons with Down’s syndrome

In persons with Down’s syndrome (DS) immunological abnormalities as well as hypothyroidism and Alzheimer type dementia are frequently observed. In addition, the activity of the enzyme cystathionine beta-synthase (CBS) is over-expressed which results in an altered homocysteine metabolism

Effects of interferon-alpha on the inflammatory response of swine peripheral blood mononuclear cells

Interferon-\u3b1 (IFN-\u3b1) at low concentrations had been previously shown to control the expression of inflammatory cytokine genes in swine pulmonary alveolar macrophages. In the first part of this study, cultured swine peripheral blood mononuclear cells (PBMCs) were supplemented with IFN-\u3b1 at low/moderate concentrations, and then stimulated with lipopolysaccharide (LPS). The expression of IFN-\u3b1, IFN-\u3b3, IL-1\u392, TNF-\u3b1, and IL-6 genes was determined by real-time PCR. IFN-\u3b1 at low/moderate concentrations did not significantly reduce the expression of any cytokine gene under study, with clear trends though to a concentration-dependent reduction of IL-1\u392 gene expression and to a concentration-dependent increase of IFN-\u3b3 gene expression. In vivo, orally administered IFN-\u3b1 was shown instead to modulate the inflammatory response to early weaning in uncultured PBMCs of specific pathogen-free piglets. As opposed to the in vitro model, the oral IFN-\u3b1 treatment reduced after weaning the expression of the IFN-\u3b3 gene (P < 0.08) and increased that of the IL-1\u392 gene (P < 0.05). There was also a trend to a reduced expression of both IL-6 and TNF-\u3b1. The above modulation of cytokine genes expression and the greater daily mean weight gain of treated piglets highlight important regulatory properties of oral IFN-\u3b1 in the response to the weaning stress

Lymphomonocyte alpha-synuclein levels in aging and in Parkinson disease

In this study we employed an ELISA assay to measure alpha-synuclein protein in lymphomonocytes from 78 PD patients and 78 controls. We correlated protein levels with demographic and clinical characteristics and with the chymotryptic and tryptic activities of the 20S proteasome. Alpha-synuclein levels were not significantly different between patients and controls. In control subjects, alpha-synuclein protein levels increased significantly with age and were significantly higher in men compared to women. Proteasome activity was not significantly different between cases and controls. In control group, the 20S chymotryptic activity tended to decrease significantly with increasing age, though it was not correlated to alpha-synuclein levels. The 20S tryptic activity was not significantly correlated to age, but was inversely correlated to alpha-synuclein levels. Our findings suggest that alpha-synuclein levels in lymphomonocytes are affected by age, gender, and by the 20S proteasome activity in control subjects, but they are not useful as a diagnostic biomarker for PD

Prenatal N-acetyl-cysteine administration moderates the long-term negative effects of maternal obesity in adolescent male and female mouse offspring

Obesity during pregnancy may affect offspring developmental trajectories representing a risk factor for mental health. Amongst the mechanisms called into question inflammation, oxidative stress and the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis appear as the most suitable. We investigated the emotional phenotype of male and female offspring of dams exposed to a high-fat diet (HFD, a mouse model of maternal obesity) before and during pregnancy. We also tested the efficacy of N-acetyl-cysteine (NAC – an antioxidant) in preventing the negative effects of HFD. We focused on adolescence, an age of main vulnerability for the onset of psychopathologies. Female C57BL/6N mice were fed HFD for 13 weeks and, after 5 weeks, were also exposed to NAC (1 g/kg b.w.) via drinking water, until delivery. Emotionality was assessed in 35-45-day-old adolescent mice by means of the elevated-plus-maze (EPM) and social interaction tests (SIT). A forced swimming test was used both to evaluate depressive-like behaviour as well as a stressful challenge to measure HPA axis reactivity. NAC was effective in moderating body weight gain in HFD-treated dams. Prenatal HFD reduced exploratory behaviours in the EPM in periadolescent offspring; NAC administration resulting in increased social interactions in the offspring of HFD dams. Analyses of depression-like behaviours, HPA axis functionality and brain transcriptomics are currently ongoing for mechanistic insight. Data from these studies indicate that the long-term effects of maternal obesity may be mediated by changes in oxidative stress and point to NAC as a potential preventive strategy. ERANET-NEURON-JTC 2018 (Mental Disorders) Project ‘‘EMBED”

Oxidative stress in peripheral blood mononuclear cells from patients with Parkinson's disease: negative correlation with levodopa dosage

Oxidative stress, resulting from the imbalance between reactive oxygen species (ROS) formation and antioxidant defenses, plays a major role in the pathogenesis of Parkinson's disease (PD). However, the contribution of levodopa (LD) therapy to oxidative damage is still debated. We investigated oxidative stress in peripheral blood mononuclear cells (PBMCs) from LD-treated PD patients and healthy subjects. Increased ROS production associated with unaltered glutathione reductase activity was detected in PBMC from PD patients. LD daily dosage appeared to be inversely correlated with ROS levels and positively associated with GR activity, suggesting a protective role for LD on PBMCs redox status. Our data support the view of systemic oxidative stress involvement in PD and give further rationale for using PBMCs as an easily accessible ex-vivo dopaminergic model for exploring the biological effects of LD therapy

N-acetyl-cysteine administration during foetal life improves social behaviour and restores hippocampal BDNF levels in adolescent mice prenatally exposed to a high-fat diet

Maternal obesity may affect foetal programming representing a risk for adult mental health. Oxidative stress and inflammation associated with maternal obesity can alter the maturation of neuronal circuits affecting behaviour and mood. We investigated the emotional phenotype of male and female mouse offspring born from a high-fat diet (HFD) fed dams. We also tested the efficacy of N-acetyl-cysteine (NAC – an antioxidant) in preventing the negative effects of HFD. We focused on adolescence, an age of main vulnerability for the onset of psychopathology. Female C57BL/6N mice were fed HFD for 13 weeks and, after 5 weeks, were also exposed to NAC (1 g/kg b.w.) via drinking water, until delivery. The neurodevelopment of offspring was assessed through the homing test. Emotionality was assessed in 35-45-day-old adolescent mice through elevated-plus-maze (EPM) and social interaction tests (SIT). Transcriptomic analysis of hippocampal tissue were performed to identify mechanisms of action of both HFD and NAC. NAC was effective in moderating body weight gain in HFD-fed dams. Neither HFD or NAC affected offspring development. Regardless of sex, prenatal HFD reduced exploration and decreased sociability, in EPM and SIT respectively. Prenatal HFD decreased hippocampal levels of BDNF in female offspring. Prenatal NAC administration prevented social anxiety and restored BDNF levels in the HFD group. Data indicate long-term effects of maternal obesity on dams’ weight, offspring’s behaviour and hippocampal BDNF levels. These effects may be mediated by changes in oxidative stress as NAC was effective as a preventive agent. ERANET-NEURON-JTC 2018 (Mental Disorders) Project “EMBED”