Alpha-synuclein nitration and autophagy response are induced in peripheral blood cells from patients with Parkinson disease.

Several lines of evidence implicate a central role for alpha-synuclein (aSN) in the pathogenesis of Parkinson's disease (PD). Besides rare genetic mutations, post-translational mechanisms, such as oxidative stress-related nitration, may alter the protein properties in terms of propensity to aggregate or be degraded. Our group previously described increased reactive oxygen species (ROS) production within easily accessible peripheral blood mononuclear cells (PBMCs) in PD patients compared to healthy elderly subjects.

Neuroligand binding endophenotypes in blood cells distinguish two subsets of borderline personality disorder patients.

Neurotransmitter ligand binding in blood cells was assessed in borderline personality disorder (BDP) patients, testing the possibility that different biochemical endophenotypes might lie beneath a specific clinical presentation. The density of peripheral benzodiazepine receptors (PBR) and serotonin transporters were assessed in peripheral blood mononuclear cells (PBMC) and platelets, respectively, showing a decrease of both parameters. Moreover, a further significant decrease of PBR in PBMC was shown for those patients with a depressive trait.

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

Interferon-α (IFN-α) 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-α at low/moderate concentrations, and then stimulated with lipopolysaccharide (LPS). The expression of IFN-α, IFN-γ, IL-1β, TNF-α, and IL-6 genes was determined by real-time PCR.

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.

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.

Substrate-induced modulation of glutamate uptake in human platelets.

In the central nervous system (CNS), glutamate rapidly upregulates the activities of different excitatory amino-acid transporter subtypes (EAATs) in order to help protect neurons from excitotoxicity. Since human platelets display a specific sodium-dependent glutamate uptake activity, and express the three major glutamate transporters, which may be affected in neurological disorders, we investigated whether platelets are subject to substrate-induced modulation as described for CNS. A time- and dose-dependent upregulation of [3H]-glutamate uptake (up to two-fold) was observed in platelets preincubated with glutamate.

Effects of IFN-alpha on the inflammatory response of swine leukocytes to bacterial endotoxin.

Because low-dose interferon-alpha (IFN-alpha) treatment had proved effective in several models of chronic inflammation and autoimmune disease, a possible role of IFN-alpha in modulating the response of swine leukocytes to bacterial endotoxin was investigated in this study. Exposure of swine peripheral blood mononuclear cells (PBMC) to low concentrations of human IFN-alpha caused a strong, dose-dependent decrease in CD14 expression, the lowest level being observed at 5 U/ml IFN-alpha. This result was confirmed if PBMC were later exposed to purified lipopolysaccharide (LPS).

Fibroblast glutamate transport in aging and in AD: correlations with disease severity.

Altered glutamate transport and aberrant EAAT1 expression were shown in Alzheimer's disease (AD) brains. It is presently unknown whether these modifications are a consequence of neurodegeneration or play a pathogenetic role. However, recent findings of decreased glutamate uptake, EAAT1 protein and mRNA in AD platelets suggest that glutamate transporter modifications may be systemic and might explain the decreased glutamate uptake.

Increased plasma glutamate in stroke patients might be linked to altered platelet release and uptake.

Experimental studies have shown the role of excitotoxicity in the pathogenesis of ischemic brain lesions, and glutamate levels have been found to be elevated in CSF and plasma from patients, early after stroke. In this study, we investigated whether platelets could be involved in the mechanism of altered plasma glutamate levels after stroke. Forty four patients, from 6 hours to 9 months after ischemic stroke, 15 age-related healthy controls and 15 controls with stroke risk factors or previous transient ischemic attack were enrolled.

Oxidative stress impairs glutamate uptake in fibroblasts from patients with Alzheimer's disease.

Oxidative stress has been demonstrated in Alzheimer's disease (AD) brain and may affect glutamate transport (GT), thereby leading to excitotoxic neuronal death. Since oxidative stress markers have been shown also in peripheral tissues, we investigated possible GT alterations in fibroblast cultures obtained from 18 patients with AD and 15 control patients and analyzed the effects of the lipoperoxidation product 4-hydroxynonenal (4-HNE) and antioxidants. Basal GT was decreased by 60% in fibroblasts from patients with AD versus control patients.

Pharmacological manipulation of glutamate transport.

L-Glutamic acid acts as the major excitatory neurotransmitter and, at the same time, represents a potential neurotoxin for the mammalian central nervous system (CNS). The termination of excitatory transmission and the maintenance of physiologic levels of extracellular glutamate, which is necessary to prevent excitotoxicity, are prominently mediated by a family of high-affinity sodium-dependent excitatory amino acid transporters (EAATs). Five subtypes of EAATs have been cloned, possessing distinct pharmacology, localization, sensitivity to transport inhibitors and modulatory mechanisms.

Altered glutamate uptake in peripheral tissues from Down syndrome patients.

Overexpression of APP and SOD induces beta-amyloid deposition and oxidative stress in Down syndrome (DS) patients. Both phenomena may impair glutamate transport and decreased glutamate uptake sites have been demonstrated in patient brains at autopsy. Since alterations of APP metabolism and oxidative damage are systemic, we investigated glutamate uptake in platelets and fibroblasts from DS patients to explore whether abnormalities in this process are inherent properties of DS cells and not secondary to neurodegeneration.