Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination

Abstract Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Did the movie Joker portray mental illness correctly and does it matter? We passionately go over the movie Joker from the lense of people living with mental illness and discuss whether or not there are implications of making a movie like this. Does it help us or hurt us? What if it does both? Listen in to hear Gabe’s freakishly good recollection of scenes from the movie as Jackie struggles to separate entertainment from reality.  Spoiler Alert: You don’t need to see Joker to appreciate this conversation but we do go over the plot and reveal some important scenes from the movie. (Transcript Available Below)...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: A Bipolar, A Schizophrenic, and a Podcast Antidepressant Antipsychotic Depression Minding the Media Not Crazy Podcast Source Type: blogs
Publication date: Available online 12 October 2019Source: Multiple Sclerosis and Related DisordersAuthor(s): Shahin Khayambashi, Amber Salter, Tuula Tyry, Gary R Cutter, Robert J Fox, Ruth Ann MarrieAbstractObjectiveWe aimed to determine the association between gender identity and sexual orientation on healthcare-related utilization in persons with multiple sclerosis (MS), as well as satisfaction with their doctor and comfort discussing sexual health with their doctor.MethodsWe surveyed participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding their gender identity and sexua...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
ConclusionsThere is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.
Source: CNS Drugs - Category: Neurology Source Type: research
In this study the effect of EAon muscle dysfunction, its mitochondria, and Sirt3 enzyme incuprizone-induced model of MSwas examined.Demyelination was induced by a diet containing 0.2% w/w cuprizone (Cup) for 42 days and EA administered daily (5, 50, and 100 mg/kg P.O) either with or without cuprizone in mice. Behavioral tests were assessed, and muscle tissue markers ofoxidative stress, mitochondrial parameters, mitochondrial respiratory chain activity, the Sirt3 protein level, and Sirt3 expression were also determined.Luxol fast blue staining and the behavioral tests were performed toassess the implemented model. In Cup ...
Source: Life Sciences - Category: Biology Source Type: research
The objectives were to study the expression of very late antigen (VLA)-4, melanoma cell adhesion molecule-1 (MCAM-1) and activated leukocyte cell adhesion molecule (ALCAM) on CD4+ T cells during natalizumab treatment and to investigate the association with disease activity.We find that subgroups of autoreactive T cells are retained in peripheral blood, in particular MOG-reactive CD4+ T cells expressing MCAM-1. The expression of MCAM-1 or ALCAM on CD4+ T cells was, however, not clearly associated with disease activity (clinical or MRI) during natalizumab treatment.
Source: Journal of Neuroimmunology - Category: Allergy & Immunology Authors: Source Type: research
Authors: Goodman A, Anadani N, Gerwitz L Abstract Introduction: Multiple sclerosis (MS) causes focal lesions of immune-mediated demyelinating events followed by slow progressive accumulation of disability. Over the past 2 decades, multiple medications have been studied and approved for use in MS. Most of these agents work by modulating or suppressing the peripheral immune system. Siponimod is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator which internalizes S1P1 receptors thereby inhibiting efflux of lymphocytes from lymph nodes and thymus. There are promising data suggesting that it may also h...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
The present study examined the relationships among parameters (i.e., volume and pattern) of physical activity and sedentary behavior with the presence and severity of restless legs syndrome(RLS) in adults with multiple sclerosis(MS). Participants with MS (N  = 253) wore an accelerometer for a 7-day period and completed the Cambridge-Hopkins Restless Legs Syndrome Questionnaire, the International Restless Legs Syndrome Study Group Scale (IRLS), and the Patient Determined Disease Steps scale. Sixty-six (26%) persons with MS had RLS (MS + RLS).
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Source Type: research
Publication date: Available online 10 October 2019Source: Life SciencesAuthor(s): Yam Nath Paudel, Efthalia Angelopoulou, Bhuvan K. C, Christina Piperi, Iekhsan OthmanAbstractMultiple sclerosis (MS) is an autoimmune chronic inflammatory disease with distinctive features of focal demyelination, axonal loss, activation of glial cells, and immune cells infiltration. The precise molecular mechanism underlying the disease progression remains enigmatic despite of the rapid progression on experimental and clinical MS research. The focus of MS therapy relies on the repression of the pathogenic autoimmune response without compromis...
Source: Life Sciences - Category: Biology Source Type: research
FRIDAY, Oct. 11, 2019 -- Reduction in peripapillary retinal nerve fiber layer (pRNFL) thickness is significantly associated with physical and cognitive disability in patients with multiple sclerosis (MS), according to a study published in the...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
CONCLUSION: disease duration was strongly correlated with a higher number of disabilities and better socioeconomic and educational profiles showed to be protective factors for functionality. Care planning should consider the needs observed by the multidisciplinary team, stimulating the development of self-care, functionality and sociability. PMID: 31596417 [PubMed - in process]
Source: Revista Latino-Americana de Enfermagem - Category: Nursing Authors: Tags: Rev Lat Am Enfermagem Source Type: research
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