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Toll-like receptor expression in the blood and brain of patients and a mouse model of Parkinson's disease

BACKGROUND: Accumulating evidence supports a role for the immune system in the pathogenesis of Parkinson's disease. Importantly, recent preclinical studies are now suggesting a specific contribution of inflammation to the α-synuclein-induced pathology seen in this condition.METHODS: We used flow cytometry and western blots to detect toll-like receptor 2 and 4 expression in blood and brain samples

Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling

Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we su

The potential of alternate sources of cells for neural grafting in Parkinson's and Huntington's disease

Cell-based therapies for Parkinson's and Huntington's disease have provided mixed clinical outcomes and one of the reasons underlying this is the use of primary fetal tissue as the source of grafted cells. An alternate source of cells, such as stem cells, could overcome many of the issues associated with primary fetal tissue and would help bring forward cell replacement therapy as a reliable and e

The challenges of administering cell-based therapies to patients with Parkinson's disease

Although the concept of cell-based therapy for Parkinson's disease has been around for more than three decades with proof-of-concept studies in man having been achieved, it still remains a controversial experimental therapy. In this review, we discuss the reasons for this and the challenges that this approach generates in the treatment of Parkinson's disease in terms of adopting better strategies

Brain bioavailability of human intravenous immunoglobulin and its transport through the murine blood-brain barrier

Intravenous immunoglobulin (IVIg) is currently evaluated in clinical trials for the treatment of various disorders of the central nervous system. To assess its capacity to reach central therapeutic targets, the brain bioavailability of IVIg must be determined. We thus quantified the passage of IVIg through the blood-brain barrier (BBB) of C57Bl/6 mice using complementary quantitative and qualitati

Parkinson's Disease in a Dish : What Patient Specific-Reprogrammed Somatic Cells Can Tell Us about Parkinson's Disease, If Anything?

Technologies allowing for the derivation of patient-specific neurons from somatic cells are emerging as powerful in vitro tools to investigate the intrinsic cellular pathological behaviours of the diseases that affect these patients. While the use of patient-derived neurons to model Parkinson's disease (PD) has only just begun, these approaches have allowed us to begin investigating disease pathog

Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson's disease

Intravenous immunoglobulin (IVIg) is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson's disease (PD), we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg) at 2-hour i

Inflammation and neurodegeneration : the story 'retolled'

Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to the pathophysiology of Alzheimer's disease (AD), Parkinson's disease (PD), and rel

MyD88 deficiency results in both cognitive and motor impairments in mice

The myeloid differentiation primary response gene 88 (MyD88) product is the most common adaptor protein implicated in Toll-like and interleukin receptor (TIR) domain signaling and thus plays an important role in the innate immune system. Despite the fact that the MyD88-dependent pathway has emerged as an important player in cell death processes described in several animal models of neurodegenerati

The role of the MYD88-dependent pathway in MPTP-induced brain dopaminergic degeneration

BACKGROUND: Mounting evidence supports a significant role of inflammation in Parkinson's disease (PD) pathophysiology, with several inflammatory pathways being suggested as playing a role in the dopaminergic degeneration seen in humans and animal models of the disease. These include tumor necrosis factor, prostaglandins and oxidative-related stress components. However, the role of innate immunity

The critical role of the MyD88-dependent pathway in non-CNS MPTP-mediated toxicity

A growing body of evidence supports a role of inflammation in the loss of central nervous system neurons both to acute and chronic insults, while its contribution to the loss of neurons in the enteric nervous system remains largely uninvestigated. We have addressed this issue by exploring the role of inflammation in dopaminergic (DAergic) myenteric neuronal degeneration secondary to MPTP lesioning

Neuroinflammation is associated with changes in glial mGluR5 expression and the development of neonatal excitotoxic lesions

It has been hypothesized that neuroinflammation triggered during brain development can alter brain functions later in life. We investigated the contribution of inflammation to the alteration of normal brain circuitries in the context of neuroexcitotoxicity following neonatal ventral hippocampal lesions in rats with ibotenic acid, an NMDA glutamate receptor agonist. Excitotoxic ibotenic acid lesion

Environmental toxins and Parkinson's disease : what have we learned from pesticide-induced animal models?

Parkinson's disease (PD) is a common neurodegenerative disorder largely of idiopathic nature with the exceptions of rare familial forms, and is characterized by both motor and non-motor disturbances. Pathologically, most motor features are the result of a dramatic loss of ventral tier mesencephalic dopaminergic neurons and thus dopamine content at their target sites. Although the exact etiology of

Automatic Creation of Multilingual Semantic Networks from Wikipedia

This paper describes the automatic creation of semantic networks from Wikipedia. Following Lipczak et al. (2014), we constructed the graphs corresponding to the semantic networks by merging across languages the categories manually assigned by the users. This results in a network of related concepts for each entity of Wikipedia. We used these networks as a component of an entity linking system. the

Challenges from Integrating Usability Activities in Scrum : Why is Scrum So Fashionable?

Scrum is currently a widely used process in most areas of software development. Conversely, usability activities as prescribed in the area of HCI are not widely used in the software industry, especially not in agile software development projects. Through an analysis of interview and survey data from five studies we scrutinize the reasons for choosing Scrum, consequences of using Scrum, and study tScrum is currently a widely used process in most areas of software development. Conversely, usability activities as prescribed in the area of HCI are not widely used in the software industry, especially not in agile software development projects. Through an analysis of interview and survey data from five studies we scrutinize the reasons for choosing Scrum, consequences of using Scrum, and study t

Professionernas farhågor om införandet av eJournal inom vuxenpsykiatrin i Region Skåne

Hösten 2015 var Region Skåne först i Sverige med att lägga till patientjournaler från psykiatrin till invånartjänsten eJournal. Genom tjänsten, har alla patienter i den vuxenpsykiatriska vården i Region Skåne tillgång till sin journal via nätet. Det finns lite kunskap om hur professioner na inom den psykiatriska vården förväntar sig att deras arbete kommer att påverkas av den ökade transparens som

Can Women Have Children and a Career: IV Evidence from IVF Treatments

This paper introduces a new IV strategy based on IVF (in vitro fertilization) induced fertility variation among childless women to estimate the causal effect of having children on their career. For this purpose, we use administrative data on IVF treated women in Denmark. Because observed chances of IVF success do not depend on labor market histories, IVF treatment success provides a plausible inst