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Parkinson Disease: HELP
Articles from Miscellaneous institutions in Manchester, UK
Based on 39 articles published since 2010
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These are the 39 published articles about Parkinson Disease that originated from Miscellaneous institutions in Manchester, UK during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Dance and Parkinson's: A review and exploration of the role of cognitive representations of action. 2020

Bek, Judith / Arakaki, Aline I / Lawrence, Adam / Sullivan, Matthew / Ganapathy, Gayathri / Poliakoff, Ellen. ·Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: judith.bek@manchester.ac.uk. · Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: aline.arakaki@manchester.ac.uk. · Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: a.c.lawrence@ljmu.ac.uk. · School of Science and the Environment, E432 John Dalton Building, Manchester Metropolitan University, Oxford Road, Manchester, M16 5BH, United Kingdom. Electronic address: m.sullivan@mmu.ac.uk. · Equilibrium International, 6 Stretton Avenue, Manchester, M20 6HE, United Kingdom. Electronic address: gganapathy@equintl.com. · Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: ellen.poliakoff@manchester.ac.uk. ·Neurosci Biobehav Rev · Pubmed #31846651.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative condition that causes both sensorimotor and non-motor impairments, and there is a clear need for non-medical approaches to improve quality of life. Dance is an increasingly popular activity among people with PD, which demonstrates potential therapeutic benefits. However, findings to date have been inconsistent, and little is known about the mechanisms underlying benefits of dance in PD. In this review, we provide an overview of research into dance for people with PD. The majority of quantitative evidence is in the sensorimotor domain, but cognitive, psychological and social effects have also been reported. We consider the role of cognitive representations of action within dance through observation, imitation and imagery, which may contribute to both sensorimotor and non-motor outcomes for people with PD. Moreover, we discuss how these processes may be enhanced through dance to provide further benefits in everyday life. Finally, we propose avenues for future research to increase understanding of action representation in dance for PD, which has the potential to inform practice and maximize benefits.

2 Review Experimental animal models of Parkinson's disease: A transition from assessing symptomatology to α-synuclein targeted disease modification. 2017

Ko, Wai Kin D / Bezard, Erwan. ·Motac Neuroscience Ltd, Manchester, United Kingdom. Electronic address: d.ko@motac.com. · Motac Neuroscience Ltd, Manchester, United Kingdom; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. ·Exp Neurol · Pubmed #28764902.

ABSTRACT: With the understanding that α-synuclein plays a major role in the pathogenesis of Parkinson's disease (PD), novel animal models have been developed for conducting preclinical research in screening novel disease modifying therapies. Advancements in research techniques in α-synuclein targeted disease modification have utilised methods such as viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy Bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration. In applying these cutting-edge research tools with sophisticated trial designs in preclinical drug trials, a useful platform has emerged for developing candidate agents with disease modifying actions, promising a greater chance of success for clinical translation. In this article, we describe the transition of well-established animal models of PD symptomatology to newly developed models of PD pathogenesis, with specific focus on methods of viral-mediated and inoculation of pathogenic α-synuclein, that aim to aid scientific translation of neuroprotective strategies.

3 Review Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease. 2015

Bastide, Matthieu F / Meissner, Wassilios G / Picconi, Barbara / Fasano, Stefania / Fernagut, Pierre-Olivier / Feyder, Michael / Francardo, Veronica / Alcacer, Cristina / Ding, Yunmin / Brambilla, Riccardo / Fisone, Gilberto / Jon Stoessl, A / Bourdenx, Mathieu / Engeln, Michel / Navailles, Sylvia / De Deurwaerdère, Philippe / Ko, Wai Kin D / Simola, Nicola / Morelli, Micaela / Groc, Laurent / Rodriguez, Maria-Cruz / Gurevich, Eugenia V / Quik, Maryka / Morari, Michele / Mellone, Manuela / Gardoni, Fabrizio / Tronci, Elisabetta / Guehl, Dominique / Tison, François / Crossman, Alan R / Kang, Un Jung / Steece-Collier, Kathy / Fox, Susan / Carta, Manolo / Angela Cenci, M / Bézard, Erwan. ·Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Department of Neurology, University Hospital Bordeaux, France. · Laboratory of Neurophysiology, Fondazione Santa Lucia, IRCCS, Rome, Italy. · Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy. · Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. · Department of Neurology, Columbia University, New York, USA. · Pacific Parkinson's Research Centre and National Parkinson Foundation Centre of Excellence, University of British Columbia, Vancouver, Canada. · Department of Biomedical Sciences, Section of Neuropsychopharmacology, Cagliari University, 09124 Cagliari, Italy. · Univ. de Bordeaux, Institut Interdisciplinaire de neurosciences, UMR 5297, 33000 Bordeaux, France; CNRS, Institut Interdisciplinaire de neurosciences, UMR 5297, 33000 Bordeaux, France. · Department of Neurology, Hospital Universitario Donostia and Neuroscience Unit, Bio Donostia Research Institute, San Sebastian, Spain. · Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · Center for Health Sciences, SRI International, CA 94025, USA. · Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy. · Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy. · Department of Biomedical Sciences, Physiology Section, Cagliari University, Cagliari, Italy. · Motac Neuroscience Ltd, Manchester, UK. · Michigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA. · Morton & Gloria Shulman Movement Disorders Center, Toronto Western Hospital, Toronto, Ontario M4T 2S8, Canada. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Motac Neuroscience Ltd, Manchester, UK. Electronic address: erwan.bezard@u-bordeaux.fr. ·Prog Neurobiol · Pubmed #26209473.

ABSTRACT: Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.

4 Review Why bother using non-human primate models of cognitive disorders in translational research? 2015

Camus, Sandrine / Ko, Wai Kin D / Pioli, Elsa / Bezard, Erwan. ·Motac Neuroscience Ltd, Manchester, United Kingdom. · Motac Neuroscience Ltd, Manchester, United Kingdom; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. ·Neurobiol Learn Mem · Pubmed #26135120.

ABSTRACT: Although everyone would agree that successful translation of therapeutic candidates for central nervous disorders should involve non-human primate (nhp) models of cognitive disorders, we are left with the paucity of publications reporting either the target validation or the actual preclinical testing in heuristic nhp models. In this review, we discuss the importance of nhps in translational research, highlighting the advances in technological/methodological approaches for 'bridging the gap' between preclinical and clinical experiments. In this process, we acknowledge that nhps remain a vital tool for the investigation of complex cognitive functions, given their resemblance to humans in aspects of behaviour, anatomy and physiology. The recent improvements made for a suitable nhp model in cognitive research, including new surrogates of disease and application of innovative methodological approaches, are continuous strides for reaching efficient translation for human benefit. This will ultimately aid the development of innovative treatments against the current and future threat of neurological and psychiatric disorders to the global population.

5 Clinical Trial A mixed methods evaluation of a Mindfulness-Based Stress Reduction course for people with Parkinson's disease. 2017

Birtwell, Kelly / Dubrow-Marshall, Linda / Dubrow-Marshall, Rod / Duerden, Tim / Dunn, Annette. ·University of Salford, The Crescent, Salford M5 4WT, UK; The University of Manchester, Centre for Primary Care, Williamson Building, Oxford Rd., Manchester M13 9PL, UK. Electronic address: Kelly.birtwell@outlook.com. · University of Salford, The Crescent, Salford M5 4WT, UK. · University of Salford, The Crescent, Salford M5 4WT, UK; Integrated Mindfulness, 145 Radcliffe New Road, Whitefield, Manchester M45 7RP, UK. · Integrated Mindfulness, 145 Radcliffe New Road, Whitefield, Manchester M45 7RP, UK. ·Complement Ther Clin Pract · Pubmed #29122265.

ABSTRACT: OBJECTIVE: The aim of this study was to evaluate the effects of an 8-week Mindfulness-Based Stress Reduction course (MBSR) on people with Parkinson's disease who experienced depression, anxiety, stress or difficulty coping with Parkinson's. METHODS: Thirteen participants were recruited and six completed the full MBSR course. Data were analysed using repeated measures analysis of variance and thematic analysis. RESULTS: There were significant improvements in levels of depression, anxiety and stress at weeks eight and sixteen, as measured by the Depression Anxiety and Stress Scale, short version (DASS-21). Themes of 'mindfulness as challenging' and 'mindfulness as life-enhancing' were identified from follow-up questionnaire responses. All participants reported they would recommend MBSR to other people with Parkinson's. CONCLUSION: This study supports previous preliminary findings that mindfulness-based interventions could benefit people with Parkinson's experiencing non-motor symptoms. Further research using larger sample sizes, a control group, and a longer follow-up period is required.

6 Clinical Trial Beneficial Effects of Bilateral Subthalamic Stimulation on Non-Motor Symptoms in Parkinson's Disease. 2016

Dafsari, Haidar Salimi / Reddy, Prashanth / Herchenbach, Christiane / Wawro, Stefanie / Petry-Schmelzer, Jan Niklas / Visser-Vandewalle, Veerle / Rizos, Alexandra / Silverdale, Monty / Ashkan, Keyoumars / Samuel, Michael / Evans, Julian / Huber, Carlo A / Fink, Gereon R / Antonini, Angelo / Chaudhuri, K Ray / Martinez-Martin, Pablo / Timmermann, Lars / Anonymous940843. ·Department of Neurology, University Hospital Cologne, Cologne, Germany. Electronic address: haidar.dafsari@uk-koeln.de. · National Parkinson Foundation International Centre of Excellence, King's College Hospital, London, UK. · Department of Neurology, University Hospital Cologne, Cologne, Germany. · Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Germany. · Department of Neurology and Neurosurgery, Salford Royal Foundation Trust, Greater Manchester, UK. · Parkinson disease and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy. · National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. · Department of Neurology, University Hospital Cologne, Cologne, Germany. Electronic address: lars.timmermann@uk-koeln.de. ·Brain Stimul · Pubmed #26385442.

ABSTRACT: BACKGROUND: STN-DBS is well established to improve motor symptoms and quality of life in patients with PD. While non-motor symptoms are crucial for quality of life in these patients, only neuropsychiatric and neuropsychological symptoms have been systematically studied in a longitudinal design so far. However, these are only a part of the non-motor symptoms spectrum. HYPOTHESIS: We hypothesized that STN-DBS is associated with a beneficial effect on a range of non-motor symptoms. METHODS: In this multicenter, open, prospective, international study (EuroInf-study, UKCRN10084/DRKS00006735) we investigated non-motor effects of STN-DBS in "real-life" use. We evaluated Non-motor Symptom Scale, and Questionnaire, PD Questionnaire-8, Scales for Outcomes of PD motor examination and complications, and activities of daily living preoperatively and at 6 months follow-up in 60 consecutive patients (35 male, mean age: 61.6 ± 7.8 years, mean disease duration: 10.4 ± 4.2 years). RESULTS: All outcomes improved significantly at 6 months follow-up (PD Questionaire-8, p = 0.006; activities of daily living, p = 0.012; all others, p < 0.001; Wilcoxon signed-rank, respectively paired t-test; Bonferroni-correction). Post-hoc analyses of Non-motor Symptom Scale domains showed a significant reduction of sleep/fatigue and miscellaneous domains (p ≤ 0.001), perceptual problems/hallucinations (p = 0.036), and urinary (p = 0.018) scores. Effect sizes were "moderate" for Non-motor Symptom Scale, and motor complications, "large" for motor examination, and "small" for other outcomes. CONCLUSIONS: This study provides evidence that bilateral STN-DBS improves non-motor burden in patients with PD and opens the door to a more balanced evaluation of DBS outcomes. Further randomized studies are needed to confirm these findings and compare DBS non-motor effects to other invasive therapies of advanced PD.

7 Article Small Fibre Neuropathy in Parkinson's Disease: Comparison of Skin Biopsies from the More Affected and Less Affected Sides. 2019

Jeziorska, Maria / Atkinson, Andrew / Kass-Iliyya, Lewis / Kobylecki, Christopher / Gosal, David / Marshall, Andrew / Malik, Rayaz A / Silverdale, Monty. ·Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. · Department of Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK. · Division of Neuroscience and Experimental Psychology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. · Weill Cornell Medicine-Qatar, Doha, Qatar. ·J Parkinsons Dis · Pubmed #31381529.

ABSTRACT: We assessed small nerve fibre degeneration and regeneration in more and less affected sides in Parkinson's disease (PD). Bilateral skin biopsies from 23 PD patients were immunostained for PGP9.5 for Intraepidermal Nerve Fibre Density (IENFD) and GAP-43 for mean axonal length (MAL), total epidermal (TNFL) and subepidermal nerve fibre length (SKTNFL). IENFD (p < 0.001) and SKTNFL (p < 0.001) were lower, whilst MAL (p < 0.001) and TNFL (p < 0.05) were higher in more affected versus less affected side. These results suggest increased small nerve fibre degeneration accompanied by enhanced nerve regeneration on the side more affected by PD and GAP-43 usefulness in skin biopsy assessment.

8 Article Parkinson's-adapted cognitive stimulation therapy: a pilot randomized controlled clinical trial. 2019

Leroi, Iracema / Vatter, Sabina / Carter, Lesley-Anne / Smith, Sarah J / Orgeta, Vasiliki / Poliakoff, Ellen / Silverdale, Monty A / Raw, Jason / Ahearn, David J / Taylor, Christine / Rodda, Joanne / Abdel-Ghany, Tarek / McCormick, Sheree A. ·Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK. · Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK. · Division of Population Health, University of Manchester, Manchester, UK. · School of Health and Community Studies, Leeds Beckett University, Leeds, UK. · Division of Psychiatry, University College London, London, UK. · Salford Royal NHS Foundation Trust, Salford, UK. · Pennine Acute Hospitals NHS Trust, Oldham, UK. · Manchester University NHS Foundation Trust, Manchester, UK. · Derbyshire Healthcare NHS Foundation Trust, Kingsway, UK. · North East London NHS Foundation Trust, Rainham, UK. · North West Boroughs Healthcare NHS Foundation Trust, Warrington, UK. ·Ther Adv Neurol Disord · Pubmed #31320931.

ABSTRACT: Cognitive stimulation therapy (CST) is widely used with people with dementia, but there is no evidence of its efficacy in mild cognitive impairment or dementia in Parkinson's disease (PD-MCI; PDD) or dementia with Lewy bodies (DLB). We aimed to explore the impact of 'CST-PD', which is home-based, individualized CST adapted for this population. In a single-blind, randomized controlled exploratory pilot trial (RCT), we randomized 76 participant-dyads [PD-MCI (

9 Article Assessment of plasma creatine kinase as biomarker for levodopa-induced dyskinesia in Parkinson's disease. 2019

Delamarre, Anna / Tison, François / Li, Qin / Galitzky, Monique / Rascol, Olivier / Bezard, Erwan / Meissner, Wassilios G. ·Service de Neurologie, Hôpital Pellegrin, CHU de Bordeaux, 33000, Bordeaux, France. · Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 146 rue Léo Saignat, 33000, Bordeaux Cedex, France. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France. · Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Motac Neuroscience, Manchester, UK. · CIC Toulouse, Toulouse, France. · Départements de Pharmacologie Clinique et Neurosciences, INSERM CIC9302, CHU de Toulouse, Toulouse, France. · Service de Pharmacologie, Faculté de Médecine, CHU de Toulouse, Université de Toulouse, Toulouse, France. · Service de Neurologie, Hôpital Pellegrin, CHU de Bordeaux, 33000, Bordeaux, France. wassilios.meissner@chu-bordeaux.fr. · Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 146 rue Léo Saignat, 33000, Bordeaux Cedex, France. wassilios.meissner@chu-bordeaux.fr. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France. wassilios.meissner@chu-bordeaux.fr. · Department Medicine, University of Otago, Christchurch, New Zealand. wassilios.meissner@chu-bordeaux.fr. · New Zealand Brain Research Institute, Christchurch, New Zealand. wassilios.meissner@chu-bordeaux.fr. ·J Neural Transm (Vienna) · Pubmed #31098725.

ABSTRACT: We tested in a translational approach the usefulness of plasma creatine kinase (CK) as an objective biomarker for levodopa-induced dyskinesia (LID). Plasma CK levels were measured in five dyskinetic parkinsonian non-human primates (NHP) and in ten PD patients with LID who participated in a treatment trial with simvastatin. Plasma CK levels were increased in dyskinetic NHP and correlated with LID severity while they were not affected by LID severity in PD patients.

10 Article Increased Intraepidermal Nerve Fiber Degeneration and Impaired Regeneration Relate to Symptoms and Deficits in Parkinson's Disease. 2019

Jeziorska, Maria / Atkinson, Andrew / Kass-Iliyya, Lewis / Javed, Saad / Kobylecki, Christopher / Gosal, David / Marshall, Andrew / Silverdale, Monty / Malik, Rayaz A. ·Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom. · Department of Neurology, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom. · Division of Neuroscience and Experimental Psychology, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom. · Department of Clinical Neurophysiology, Central Manchester NHS Foundation Trust, Manchester, United Kingdom. · Weill Cornell Medicine-Qatar, Doha, Qatar. ·Front Neurol · Pubmed #30837937.

ABSTRACT:

11 Article NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology. 2019

Mellone, Manuela / Zianni, Elisa / Stanic, Jennifer / Campanelli, Federica / Marino, Gioia / Ghiglieri, Veronica / Longhi, Annalisa / Thiolat, Marie-Laure / Li, Qin / Calabresi, Paolo / Bezard, Erwan / Picconi, Barbara / Di Luca, Monica / Gardoni, Fabrizio. ·Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Università degli Studi di Milano - La Statale, 20133 Milano, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, 00100 Rome, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, 00100 Rome, Italy; Department of Philosophy, Human, Social and Educational Sciences, University of Perugia, 06100 Perugia, Italy. · Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. · Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, 00100 Rome, Italy; Clinica Neurologica, Università degli studi di Perugia, Ospedale Santa Maria della Misericordia, S. Andrea delle Fratte, 06156 Perugia, Italy. · Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Experimental Neurophysiology Laboratory, IRCCS San Raffaele Pisana, University San Raffaele, Rome, Italy. · Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Università degli Studi di Milano - La Statale, 20133 Milano, Italy. Electronic address: fabrizio.gardoni@unimi.it. ·Neurobiol Dis · Pubmed #30261285.

ABSTRACT: In the striatum, specific N-methyl-d-aspartate receptor (NMDAR) subtypes are found in different neuronal cells. Spiny projection neurons (SPNs) are characterized by NMDARs expressing GluN2A and GluN2B subunits, while GluN2D is exclusively detected in striatal cholinergic interneurons (ChIs). In Parkinson's disease (PD), dopamine depletion and prolonged treatment with levodopa (L-DOPA) trigger adaptive changes in the glutamatergic transmission from the cortex to the striatum, also resulting in the aberrant function of striatal NMDARs. While modifications of GluN2A- and GluN2B-NMDARs in SPNs have been extensively documented, only few studies report GluN2D dysfunction in PD and no data are available in L-DOPA-induced dyskinesia (LID). Here we investigate the contribution of a specific NMDAR subtype (GluN2D-NMDAR) to PD and LID, and whether this receptor could represent a candidate for future pharmacological interventions. Our results show that GluN2D synaptic abundance is selectively augmented in the striatum of L-DOPA-treated male parkinsonian rats displaying a dyskinetic phenotype. This event is associated to a dramatic increase in GluN2D binding to the postsynaptic protein scaffold PSD-95. Moreover, immunohistochemistry and electrophysiology experiments reveal that GluN2D-NMDARs are expressed not only by striatal ChIs but also by SPNs in dyskinetic rats. Notably, in vivo treatment with a well-characterized GluN2D antagonist ameliorates the severity of established dyskinesia in L-DOPA-treated animals. Our findings support a role for GluN2D-NMDARs in LID, and they confirm that cell-type and subunit specific modifications of NMDARs underlie the pathophysiology of LID.

12 Article Meta-analysis of amantadine efficacy for improving preclinical research reliability. 2018

Stanley, Philip / Pioli, Elsa Y / Kozak, Rouba / Popiolek, Michael / Bezard, Erwan. ·Research Statistics, Pfizer Worldwide Research and Development, Cambridge, United Kingdom. · Motac Neuroscience, Manchester, United Kingdom. · Internal Medicine Research Unit, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. · Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. ·Mov Disord · Pubmed #30288778.

ABSTRACT: -- No abstract --

13 Article Multidimensional Care Burden in Parkinson-Related Dementia. 2018

Vatter, Sabina / McDonald, Kathryn R / Stanmore, Emma / Clare, Linda / Leroi, Iracema. ·1 Faculty of Biology, Medicine and Health, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom. · 2 Greater Manchester Mental Health NHS Foundation Trust, Manchester, United Kingdom. · 3 Faculty of Biology, Medicine and Health, Division of Nursing, Midwifery and Social Work, School of Health Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom. · 4 Centre for Research in Ageing and Cognitive Health, University of Exeter, Exeter, United Kingdom. ·J Geriatr Psychiatry Neurol · Pubmed #30244631.

ABSTRACT: BACKGROUND AND OBJECTIVE: Providing care to people with Parkinson-related dementia (PwPRD) may result in significant stress, strain, and burden for life partners. A common measurement of life partner burden is the Zarit Burden Interview (ZBI), which considers "burden" as a unitary concept; however, burden is highly complex and most likely comprises several dimensions. This study aimed to explore the factor structure of the ZBI in life partners of PwPRD and to examine the relationships among the emerging factors and the demographic and clinical features. METHODS: Life partners of PwPRD participated in home-based quantitative assessments and self-completed postal questionnaires. The assessment battery included ZBI, measures of relationship satisfaction, mood, stress, resilience, health, quality of life, feelings related to care provision, and sociodemographic questions. Data on PwPRDs' motor and neuropsychiatric symptom severity were also elicited in home-based assessments. RESULTS: An exploratory factor analysis (principal axis factoring) of ZBI, conducted with 127 life partners, revealed five burden dimensions: social and psychological constraints, personal strain, interference with personal life, concerns about future, and guilt. These burden factors were associated with lower relationship satisfaction, mental health, and resilience, and higher stress, anxiety, depression, resentment, negative strain, and PwPRD motor severity. In multiple linear regression analyses, where each factor score was the dependent variable, stress, negative strain, and resentment emerged as significant predictors of specific burden dimensions. CONCLUSIONS: Burden is a complex and multidimensional construct. Interventions should address specific types of burden among life partners of PwPRD to support couples' relationships and maintain quality of life.

14 Article An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates. 2018

Charvin, Delphine / Di Paolo, Therese / Bezard, Erwan / Gregoire, Laurent / Takano, Akihiro / Duvey, Guillaume / Pioli, Elsa / Halldin, Christer / Medori, Rossella / Conquet, François. ·Prexton Therapeutics SA, 1228 Plan-les-Ouates, Geneva, Switzerland. · Neuroscience Research Unit CHU de Québec, CHUL Pavillon and Faculty of Pharmacy, Laval University, Quebec City, Quebec, Canada. · Motac Neuroscience Ltd, Manchester, United Kingdom. · Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm, Sweden. ·Mov Disord · Pubmed #30216534.

ABSTRACT: BACKGROUND: Levodopa remains the gold-standard treatment for PD. However, it becomes less effective as the disease progresses and produces debilitating side effects, such as motor fluctuations and l-dopa-induced dyskinesia. Modulation of metabotropic glutamate receptor 4 represents a promising antiparkinsonian approach in combination with l-dopa, but it has not been demonstrated in primates. OBJECTIVE: We studied whether a novel positive allosteric modulator of the metabotropic glutamate receptor 4, PXT002331 (foliglurax), could reduce parkinsonism in primate models. METHODS: We assessed the therapeutic potential of PXT002331 in three models of MPTP-induced parkinsonism in macaques. These models represent three different stages of disease evolution: early stage and advanced stage with and without l-dopa-induced dyskinesia. RESULTS: As an adjunct to l-dopa, PXT002331 induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced dyskinesia. PXT002331 brain penetration was also assessed using PET imaging in macaques, and pharmacodynamic analyses support target engagement in the therapeutic effects of PXT002331. CONCLUSIONS: This work provides a demonstration that a positive allosteric modulator of metabotropic glutamate receptor 4 can alleviate the motor symptoms of PD and the motor complications induced by l-dopa in primates. PXT002331 is the first compound of its class to enter phase IIa clinical trials. © 2018 International Parkinson and Movement Disorder Society.

15 Article The expression of cannabinoid type 1 receptor and 2-arachidonoyl glycerol synthesizing/degrading enzymes is altered in basal ganglia during the active phase of levodopa-induced dyskinesia. 2018

Rojo-Bustamante, Estefania / Abellanas, Miguel Angel / Clavero, Pedro / Thiolat, Marie-Laure / Li, Qin / Luquin, Maria Rosario / Bezard, Erwan / Aymerich, Maria S. ·Universidad de Navarra, Facultad de Ciencias, Departamento de Bioquímica y Genética, Avenida Pío XII, 31008 Pamplona, Spain; Universidad de Navarra, CIMA, Programa de Neurociencias, Avenida Pío XII, 31008 Pamplona, Spain. · Servicio de Neurología, Complejo Hospitalario de Navarra, Pamplona, Spain; IdiSNA, Instituto de Investigación Sanitaria de Navarra, Spain. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. · Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Universidad de Navarra, CIMA, Programa de Neurociencias, Avenida Pío XII, 31008 Pamplona, Spain; IdiSNA, Instituto de Investigación Sanitaria de Navarra, Spain; Clínica Universidad de Navarra, Servicio de Neurología, Avenida Pío XII, 31008 Pamplona, Spain. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Universidad de Navarra, Facultad de Ciencias, Departamento de Bioquímica y Genética, Avenida Pío XII, 31008 Pamplona, Spain; Universidad de Navarra, CIMA, Programa de Neurociencias, Avenida Pío XII, 31008 Pamplona, Spain; IdiSNA, Instituto de Investigación Sanitaria de Navarra, Spain. Electronic address: maymerich@unav.es. ·Neurobiol Dis · Pubmed #29936234.

ABSTRACT: Management of levodopa-induced dyskinesias (LID) is one of the main challenges in the treatment of Parkinson's disease patients. Mechanisms involved in the appearance of these involuntary movements are not well known but modifications in the activity of different neurotransmitter pathways seem to play an important role. The objective of this study was to determine differences in the expression levels of the endocannabinoid system (ECS) elements that would support a role in LID. The basal ganglia nuclei, putamen, external segment of the globus pallidus (GPe), internal segment of the globus pallidus (GPi), subthalamic nucleus (STN) and substantia nigra (SN) were dissected out from cryostat sections obtained from two groups of parkinsonian monkeys treated with levodopa to induce dyskinesias. One group of dyskinetic animals was sacrificed under the effect of levodopa, during the active phase of LID, and the other group 24 h after the last levodopa dose (OFF levodopa). Biochemical analysis by real-time PCR for ECS elements was performed. CB

16 Article A qualitative study of female caregiving spouses' experiences of intimate relationships as cognition declines in Parkinson's disease. 2018

Vatter, Sabina / McDonald, Kathryn R / Stanmore, Emma / Clare, Linda / McCormick, Sheree A / Leroi, Iracema. ·Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK. · Research and Innovation, Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK. · Division of Nursing, Midwifery & Social Work, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK. · Centre for Research in Ageing and Cognitive Health (REACH), School of Psychology, University of Exeter, Exeter, UK. · PenCLAHRC, Institute of Health Research, University of Exeter Medical School, UK. ·Age Ageing · Pubmed #29617933.

ABSTRACT: BACKGROUND: the complex and progressive nature of Parkinson's disease (PD) and cognitive impairment may necessitate a care provider, a role which is frequently undertaken by a spouse. Providing and receiving care related to dementia impacts on a couple's partnership and may result in decreased intimacy and relationship satisfaction. OBJECTIVE: to explore the changes in long-term intimate relationships in Parkinson's-related dementia, as perceived by spouses providing care to their partners. METHODS: participants were identified using purposive sampling. Twelve female spouses whose partners had PD and mild cognitive impairment (PD-MCI), PD dementia (PDD) or dementia with Lewy bodies (DLB) completed semi-structured face-to-face interviews. Transcribed data were analysed using inductive thematic analysis. The consolidated criteria for reporting qualitative research (COREQ) were applied. RESULTS: couples' relationship satisfaction, intimacy and communication had already reduced in the mild cognitive impairment stage of PD, but the decline in these domains was markedly greater with the emergence of dementia. Increased spousal care responsibilities resulted in partners spending more time together, but feeling emotionally more distanced. Several participants' roles transitioned from spouse to caregiver and they reported feelings of frustration, resentment, anger, sadness and a worry for the future. Cognitive impairment was significantly harder to accept, manage and cope with than the motor symptoms of PD. Spouses acknowledged their marital commitments and exhibited acceptance, adjustment, resilience and various coping strategies. CONCLUSION: this is the first study exploring relationship satisfaction in Parkinson's-related dementia and has provided valuable insight into the changing patterns of intimate relationships.

17 Article Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo. 2018

Frøyset, Ann Kristin / Edson, Amanda J / Gharbi, Naouel / Khan, Essa A / Dondorp, Daniel / Bai, Qing / Tiraboschi, Ettore / Suster, Maximiliano L / Connolly, Joanne B / Burton, Edward A / Fladmark, Kari E. ·Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway. · Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA. · Neural Circuits and Behaviour Group, Uni Research AS, Bergen N-5020, Norway. · Waters Corporation, Wilmslow, Manchester, UK. · Department of Biological Sciences, University of Bergen, Bergen N-5020, Norway. Electronic address: kari.fladmark@uib.no. ·Redox Biol · Pubmed #29525604.

ABSTRACT: DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP

18 Article Psychosocial therapy for Parkinson's-related dementia: intervention development. 2017

McCormick, Sheree A / McDonald, Kathryn R / Vatter, Sabina / Orgeta, Vasiliki / Poliakoff, Ellen / Smith, Sarah J / Leroi, Iracema. ·Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK. · Manchester Academic Health Science Center (MAHSC), Manchester, UK. · Greater Manchester Mental Health Foundation Trust, Manchester, UK. · Division of Psychiatry, University College London, London, UK. · Faculty of Health Studies, University of Bradford, Bradford, UK. ·Clin Interv Aging · Pubmed #29118576.

ABSTRACT: Background: Group-based psychosocial therapy, such as group Cognitive Stimulation Therapy, improves cognition and quality of life in people living with dementia. Neuropsychiatric symptoms and restricted mobility are common complications for people with Parkinson's-related dementia (PRD) and may limit access to, and participation in, group activities. This study describes the development of a condition-specific, home-based psychosocial therapy for people with PRD ready to be trialled in a clinical population. Methods: By means of a multistage process, a draft therapy manual was developed in an iterative manner through collaboration with medical experts, researchers and Patient and Public Involvement (PPI) representatives. In stage 1, an extensive literature search of psychosocial therapies for dementia with potential relevance for Parkinson's disease (PD) was undertaken to select a candidate therapy for adaptation. In stage 2, qualitative feedback from stakeholders and intelligence regarding existing nonpharmacological therapies for cognitive impairment in PD was combined to produce a prototype therapy manual. In stage 3, the manual was field tested in: 1) a home-setting using a 25-item assessment tool; and 2) at a local PD support group with PPI representatives. Based on the feedback from this phase, final design modifications were implemented and a draft therapy manual produced. Results: The manual was developed in an iterative manner. Interview and focus group transcripts identified three enduring themes: manual form and content, therapy acceptability by people with PRD, and companion guidance and support. Major adaptations included: removal of discrete levels of task complexity, removal of images that were potentially hallucinogenic or lacked clarity, and updating of the content. Conclusion: We have successfully developed a Cognitive Stimulation Therapy-based psychosocial therapy specifically adapted for people with PRD. The therapy is ready to trial in a pilot randomized controlled study.

19 Article Parkinson's disease: summary of updated NICE guidance. 2017

Rogers, Gabriel / Davies, Debbie / Pink, Joshua / Cooper, Paul. ·National Institute for Health and Care Excellence, Manchester M1 4BT, UK Gabriel.Rogers@nice.org.uk. · Aneurin Bevan Health Board, Newport, UK. · National Institute for Health and Care Excellence, Manchester M1 4BT, UK. · Greater Manchester Neuroscience Centre, Salford, UK. · University of Manchester, Manchester, UK. ·BMJ · Pubmed #28751362.

ABSTRACT: -- No abstract --

20 Article Decreased Rhes mRNA levels in the brain of patients with Parkinson's disease and MPTP-treated macaques. 2017

Napolitano, Francesco / Booth Warren, Emily / Migliarini, Sara / Punzo, Daniela / Errico, Francesco / Li, Qin / Thiolat, Marie-Laure / Vescovi, Angelo Luigi / Calabresi, Paolo / Bezard, Erwan / Morelli, Micaela / Konradi, Christine / Pasqualetti, Massimo / Usiello, Alessandro. ·Ceinge Biotecnologie Avanzate, Naples, Italy. · Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy. · Department of Pharmacology, Vanderbilt University, Nashville, TN, United States of America. · Department of Biology Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy. · Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Italy. · Motac Neuroscience, UK-M15 6WE, Manchester, United Kingdom. · Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Université de Bordeaux, Institut des Maladies Neurodégénératives,Bordeaux, France. · Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. · IRCSS Casa Sollievo della Sofferenza, ISBReMIT-Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies, San Giovanni Rotondo, Italy. · Department of Medicine, University of Perugia and Clinica Neurologica, Santa Maria della Misericordia Hospital, Perugia, Italy. · National Research Council of Italy (CNR), Neuroscience Institute, Cagliari, Italy. · Department of Biomedical Sciences, section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy. · Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, TN, Italy. · Neuroscience Institute, National Research Council (CNR), Pisa, Italy. ·PLoS One · Pubmed #28742811.

ABSTRACT: In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples). Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.

21 Article A preclinical study on the combined effects of repeated eltoprazine and preladenant treatment for alleviating L-DOPA-induced dyskinesia in Parkinson's disease. 2017

Ko, Wai Kin D / Li, Qin / Cheng, Long Yun / Morelli, Micaela / Carta, Manolo / Bezard, Erwan. ·Motac Neuroscience Ltd, Manchester, United Kingdom. Electronic address: d.ko@motac.com. · Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Department of Biomedical Sciences, Section of Toxicology, University of Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy. · Department of Biomedical Sciences, Section of Physiology, University of Cagliari, University Campus, SS554 km 4.5, 09042 Monserrato, Italy. · Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. ·Eur J Pharmacol · Pubmed #28739086.

ABSTRACT: Eltoprazine, a serotonergic (5-HT)

22 Article Psychosocial therapy for Parkinson's-related dementia: study protocol for the INVEST randomised controlled trial. 2017

McCormick, Sheree A / McDonald, Kathryn R / Vatter, Sabina / Orgeta, Vasiliki / Poliakoff, Ellen / Smith, Sarah / Silverdale, Monty A / Fu, Bo / Leroi, Iracema. ·Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK. · Manchester Academic Health Science Centre, Manchester, UK. · Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK. · Division of Psychiatry, University College London, London, UK. · Faculty of Health Studies, University of Bradford, Bradford, UK. · Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK. ·BMJ Open · Pubmed #28630086.

ABSTRACT: INTRODUCTION: Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation. The interaction among the intervention and selected outcome measures and the efficacy of this intervention in improving cognition for people with MCI-PD, PDD or DLB will also be explored. METHODS AND ANALYSIS: Dyads will be randomised into two treatment arms to receive either 'treatment as usual' (TAU) or cognitive stimulation therapy specifically adapted for Parkinson's-related dementias (CST-PD), involving 30 min sessions delivered at home by the study companion three times per week over 10 weeks. A mixed-methods approach will be used to collect data on the operational aspects of the trial and treatment implementation. This will involve diary keeping, telephone follow-ups, dyad checklists and researcher ratings. Analysis will include descriptive statistics summarising recruitment, acceptability and tolerance of the intervention, and treatment implementation. To pilot an outcome measure of efficacy, we will undertake an inferential analysis to test our hypothesis that compared with TAU, CST-PD improves cognition. Qualitative approaches using thematic analysis will also be applied. Our findings will inform a larger definitive trial. ETHICS AND DISSEMINATION: Ethical opinion was granted (REC reference: 15/YH/0531). Findings will be published in peer-reviewed journals and at conferences. We will prepare reports for dissemination by organisations involved with PD and dementia. TRIAL REGISTRATION NUMBER: ISRCTN (ISRCTN11455062).

23 Article Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia. 2017

Bastide, Matthieu F / Glangetas, Christelle / Doudnikoff, Evelyne / Li, Qin / Bourdenx, Mathieu / Fernagut, Pierre-Olivier / Dumont, Éric C / Georges, François / Bézard, Erwan. ·Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France. · Motac neuroscience Ltd, Manchester, UK. · Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China. · Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France. erwan.bezard@u-bordeaux.fr. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France. erwan.bezard@u-bordeaux.fr. · Motac neuroscience Ltd, Manchester, UK. erwan.bezard@u-bordeaux.fr. · Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China. erwan.bezard@u-bordeaux.fr. ·Sci Rep · Pubmed #28539659.

ABSTRACT: A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson's disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons. Daun02 is a prodrug converted into Daunorubicin by ß-galactosidase. Then, the newly synthesized Daunorubicin is an inhibitor of neuronal excitability. Therefore, following induction of abnormal involuntary movements (AIMs), 6-OHDA rats were injected with Daun02 in the dlBST previously expressing ß-galactosidase under control of the FosB/ΔFosB promoter. Three days after Daun02 administration, the rats were tested daily with L-Dopa to assess LID. Pharmacogenetic inactivation of ∆FosB-expressing neuron electrophysiological activity significantly reduced AIM severity. The present study highlights the role of dlBST in the rodent analog of LID, offering a new target to investigate LID pathophysiology.

24 Article Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate. 2017

Migdalska-Richards, Anna / Ko, Wai Kin D / Li, Qin / Bezard, Erwan / Schapira, Anthony H V. ·Department of Clinical Neurosciences, Institute of Neurology, University College London, NW3 2PF, United Kingdom. · Motac Neuroscience, Manchester, United Kingdom. · Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing City, People's Republic of China. · University de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, F-33000, France. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, F-33000, France. ·Synapse · Pubmed #28295625.

ABSTRACT: Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.

25 Article The perception of affective touch in Parkinson's disease and its relation to small fibre neuropathy. 2017

Kass-Iliyya, Lewis / Leung, Matthew / Marshall, Andrew / Trotter, Paula / Kobylecki, Christopher / Walker, Susannah / Gosal, David / Jeziorska, Maria / Malik, Rayaz A / McGlone, Francis / Silverdale, Monty A. ·Greater Manchester Neuroscience Centre, Department of Neurology, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK. · Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK. · School of Natural Science & Psychology, Liverpool John Moores University, Liverpool, UK. · Institute of Human Development, University of Manchester, Manchester, UK. ·Eur J Neurosci · Pubmed #27859794.

ABSTRACT: Affective touch sensation is conducted by a sub-class of C-fibres in hairy skin known as C-Tactile (CT) afferents. CT afferents respond maximally to gentle skin stroking at velocities between 1 and 10 cm/s. Parkinson's disease (PD) is characterised by markedly reduced cutaneous C-fibres. It is not known if affective touch perception is influenced by C-fibre density and if affective touch is impaired in PD compared to healthy controls. We predicted that perceived pleasantness to gentle stroking in PD would correlate with C-afferent density and that affective touch perception would be impaired in PD compared to healthy controls. Twenty-four PD patients and 27 control subjects rated the pleasantness of brush stroking at an optimum CT stimulation velocity (3 cm/s) and two sub-optimal velocities (0.3 and 30 cm/s). PD patients underwent quantification of C-fibre density using skin biopsies and corneal confocal microscopy. All participants rated a stroking velocity of 3 cm/s as the most pleasant with significantly lower ratings for 0.3 and 30 cm/s. There was a significant positive correlation between C-fibre density and pleasantness ratings at 3 and 30 cm/s but not 0.3 cm/s. Mean pleasantness ratings were consistently higher in PD patients compared to control subjects across all three velocities. This study shows that perceived pleasantness to gentle touch correlates significantly with C-fibre density in PD. The higher perceived pleasantness in PD patients compared to controls suggests central sensitisation to peripheral inputs, which may have been enhanced by dopamine therapy.

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