Pathophysiological Changes in the Enteric Nervous System of Rotenone-Exposed Mice as Early Radiological Markers for Parkinson's Disease.

Parkinson's disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. Here we analyzed the effect of the pesticide rotenone, a mitochondrial Complex I inhibitor, on the function and neuronal composition of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression.

Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice.

Parkinson's disease is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, pathological accumulation of alpha-synuclein and motor symptoms, but also by non-motor symptoms. Metabolic abnormalities including body weight loss have been reported in patients and could precede by several years the emergence of classical motor manifestations. However, our understanding of the pathophysiological mechanisms underlying body weight loss in PD is limited.

Is there a role for ghrelin in central dopaminergic systems? Focus on nigrostriatal and mesocorticolimbic pathways.

The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer.

Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease.

The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common genetic cause of Parkinson's disease (PD). Although patients with sporadic PD and individuals with LRRK2-linked PD display the classical PD phenotype, it is not known whether or not the same biological pathways are deregulated in each context. By using transcriptome profiling, we investigated the deregulation of various biological pathways in a total of 47 peripheral blood mononuclear cell (PBMC) samples from patients with sporadic PD, patients heterozygous for the LRRK2 G2019S mutation compared to healthy controls.

Translation initiator EIF4G1 mutations in familial Parkinson disease.

Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.

Differing short-term neuroprotective effects of the fibrates fenofibrate and bezafibrate in MPTP and 6-OHDA experimental models of Parkinson's disease.

Earlier study from our group indicated that the peroxisome proliferator-activated receptor-alpha agonist fenofibrate prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell loss in C57Bl/6 mice. Our objective was to determine whether or not fibratescan improve motor activity in two experimental models of Parkinson's disease: the MPTP C57Bl/6 mouse and the 6-hydroxydopamine (6-OHDA) Wistar rat. Six groups of mice were set up: sham, sham-fenofibrate, sham-bezafibrate, MPTP, MPTP-fenofibrate and MPTP-bezafibrate.

Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation.

To gain insight into systemic molecular events associated with an age-related neurodegenerative disorder, we compared gene expression patterns in peripheral blood mononuclear cells (PBMCs) sampled from elderly, healthy controls and from Parkinson's disease (PD) patients carrying the most frequently found mutation of the LRRK2 gene (G2019S). A transcriptomic approach enabled us to detect differentially expressed genes and revealed perturbations of pathways known to be involved in PD-related neurodegeneration: the ubiquitin-proteasome system, the mitochondrial oxidation system, inflammation, axonal guidance, calcium signalling and apoptosis. Moreover, alterations of the MAP kinase pathway, the actin cytoskeleton, the ephrin receptor system and vesicular transport - all recently associated with the LRRK2 G2019S mutation pathogenesis - were noted.

Impact of prenatal stress on neuroendocrine programming.

Since life emerged on the Earth, the development of efficient strategies to cope with sudden and/or permanent changes of the environment has been virtually the unique goal pursued by every organism in order to ensure its survival and thus perpetuate the species. In this view, evolution has selected tightly regulated processes aimed at maintaining stability among internal parameters despite external changes, a process termed homeostasis. Such an internal equilibrium relies quite heavily on three interrelated physiological systems: the nervous, immune, and endocrine systems, which function as a permanently activated watching network, communicating by the mean of specialized molecules: neurotransmitters, cytokines, and hormones or neurohormones.

Prenatal stress has pro-inflammatory consequences on the immune system in adult rats.

The in utero environment is critical for initiating the ontogeny of several physiological systems, including the immune surveillance. Yet, little is known about adverse early experiences on the offspring's immunity and vulnerability to disease. The present work aimed at investigating the impact of restraint prenatal stress (PS) on the development and responsiveness of in vitro and in vivo cellular and humoral immunity of male progeny aged 7 weeks and 6 months.

Prenatal stress alters Fos protein expression in hippocampus and locus coeruleus stress-related brain structures.

Prenatal stress (PS) durably influences responses of rats from birth throughout life by inducing deficits of the hypothalamo-pituitary-adrenal (HPA) axis feedback. The neuronal mechanisms sustaining such alterations are still unknown. The purpose of the present study was to determine whether in PS and control rats, the exposure to a mild stressor differentially induces Fos protein in hippocampus and locus coeruleus, brain areas involved in the feedback control of the HPA axis.