Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles from Tokyo
Based on 723 articles published since 2010
||||

These are the 723 published articles about Parkinson Disease that originated from Tokyo during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18 · 19 · 20
401 Article Quantitative demonstration of the efficacy of night-time apomorphine infusion to treat nocturnal hypokinesia in Parkinson's disease using wearable sensors. 2016

Bhidayasiri, Roongroj / Sringean, Jirada / Anan, Chanawat / Boonpang, Kamolwan / Thanawattano, Chusak / Ray Chaudhuri, K. ·Chulalongkorn Center of Excellence for Parkinson's Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, 10330, Thailand; Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan. Electronic address: rbh@chulapd.org. · Chulalongkorn Center of Excellence for Parkinson's Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, 10330, Thailand. · Biomedical Signal Processing Laboratory, National Electronics and Computer Technology Center (NECTEC), Pathumthani, Thailand. · The Maurice Wohl Clinical Neuroscience Institute, King's College London and National Parkinson Foundation Centre of Excellence, King's College Hospital, London, United Kingdom. ·Parkinsonism Relat Disord · Pubmed #27939326.

ABSTRACT: BACKGROUND: Nocturnal hypokinesia/akinesia is one of the common night-time symptoms in patients with Parkinson's disease (PD), negatively affecting quality of life of patients and caregivers. The recognition of this problem and treatment options are limited in clinical practice. OBJECTIVES: To evaluate the efficacy of nocturnal apomorphine infusion, using a wearable sensor, in patients who are already on daytime continuous subcutaneous apomorphine infusion and still suffer from nocturnal hypokinesia. METHODS: Nocturnal parameters in 10 PD patients before and during nocturnal infusion were assessed over two nights at their homes, using a wearable sensor (trunk). Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, and number of times they got out of bed. Correlations with validated clinical rating scales were performed. RESULTS: Following nocturnal apomorphine infusion (34.8 ± 6.5 mg per night), there were significant improvements in the number of turns in bed (p = 0.027), turning velocity (p = 0.046), and the degree of turning (p = 0.028) in PD patients. Significant improvements of Modified Parkinson's Disease Sleep Scale (p = 0.005), the axial score of Unified Parkinson's Disease Rating Scale (p = 0.013), and Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.014) were also observed. CONCLUSION: Our study was able to demonstrate quantitatively the efficacy of nocturnal apomorphine infusion in PD patients with nocturnal hypokinesia and demonstrated the feasibility of using wearable sensors to yield objective and quantifiable outcomes in a clinical trial setting. More studies are needed to determine the long-term efficacy of this treatment in a large prospective cohort of PD patients.

402 Article Reward and Behavioral Factors Contributing to the Tonic Activity of Monkey Pedunculopontine Tegmental Nucleus Neurons during Saccade Tasks. 2016

Okada, Ken-Ichi / Kobayashi, Yasushi. ·Laboratories for Neuroscience, Visual Neuroscience Group, Graduate School of Frontier Biosciences, Osaka UniversityOsaka, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, Osaka UniversityOsaka, Japan. · Laboratories for Neuroscience, Visual Neuroscience Group, Graduate School of Frontier Biosciences, Osaka UniversityOsaka, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, Osaka UniversityOsaka, Japan; Research Center for Behavioral Economics, Osaka UniversityOsaka, Japan. ·Front Syst Neurosci · Pubmed #27891082.

ABSTRACT: The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined the activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our

403 Article Genetic and pharmacological correction of aberrant dopamine synthesis using patient iPSCs with BH4 metabolism disorders. 2016

Ishikawa, Taizo / Imamura, Keiko / Kondo, Takayuki / Koshiba, Yasushi / Hara, Satoshi / Ichinose, Hiroshi / Furujo, Mahoko / Kinoshita, Masako / Oeda, Tomoko / Takahashi, Jun / Takahashi, Ryosuke / Inoue, Haruhisa. ·Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan. · Sumitomo Dainippon Pharma, 3-1-98 Kasugadenaka, Konohana-ku, Osaka, Japan. · Department of Neurology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan. · School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan. · Department of Pediatrics, Okayama Medical Center, National Hospital Organization, Okayama, Japan. · Department of Neurology, Utano National Hospital, National Hospital Organization, Kyoto, Japan. ·Hum Mol Genet · Pubmed #27798097.

ABSTRACT: Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or dihydropteridine reductase (DHPR), respectively. Although BH4 metabolism disorders and its metabolisms have been studied, it is unclear how gene variants cause aberrant DA synthesis in patient neurons. Here, we generated induced pluripotent stem cells (iPSCs) from BH4 metabolism disorder patients with PTPS or DHPR variants, corrected the gene variant in the iPSCs using the CRISPR/Cas9 system, and differentiated the BH4 metabolism disorder patient- and isogenic control iPSCs into midbrain DA neurons. We found that by the gene correction, the BH4 amount, TH protein level and extracellular DA level were restored in DA neuronal culture using PTPS deficiency iPSCs. Furthermore, the pharmacological correction by BH4 precursor sepiapterin treatment also improved the phenotypes of PTPS deficiency. These results suggest that patient iPSCs with BH4 metabolism disorders provide an opportunity for screening substances for treating aberrant DA synthesis-related disorders.

404 Article Lysosomal Storage of Subunit c of Mitochondrial ATP Synthase in Brain-Specific Atp13a2-Deficient Mice. 2016

Sato, Shigeto / Koike, Masato / Funayama, Manabu / Ezaki, Junji / Fukuda, Takahiro / Ueno, Takashi / Uchiyama, Yasuo / Hattori, Nobutaka. ·Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan. · Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan. · Research Institute for Disease of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan. · Translational Research Center, Fukushima Medical University, Fukushima, Japan. · Division of Neuropathology, Department of Neuropathology, The Jikei University School of Medicine, Tokyo, Japan. · Laboratory of Proteomics and Biomolecular, Juntendo University Graduate School of Medicine, Tokyo, Japan. · Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan. · Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp. ·Am J Pathol · Pubmed #27770614.

ABSTRACT: Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid lipofuscinosis, including accumulation of lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease.

405 Article Glioblastoma Multiforme Developed during Chronic Deep Brain Stimulation for Parkinson Disease. 2016

Yamamoto, Takamitsu / Fukaya, Chikashi / Obuchi, Toshiki / Watanabe, Mitsuru / Ohta, Takashi / Kobayashi, Kazutaka / Oshima, Hideki / Yoshino, Atsuo. ·Division of Applied System Neuroscience, Nihon University School of Medicine, Tokyo, Japan. ·Stereotact Funct Neurosurg · Pubmed #27723655.

ABSTRACT: BACKGROUND: In this reported case, 7 years after the start of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN), glioblastoma multiforme (GBM) developed around the implanted DBS lead. CASE REPORT: The brain tumor formed from the subcortical white matter to the corpus callosum bilaterally around the DBS lead but did not extend in the direction of the contact points of the lead. The GBM showed a typical invasion pattern of the butterfly type. We report the first case of GBM that developed 7 years after the start of STN-DBS. CONCLUSION: Considering the low rate of GBM occurrence in association with DBS, the location of the glioma, and the pattern of tumor invasion, we speculate that GBM developed spontaneously and extended to some degree around the DBS lead. Moreover, there is a very slight possibility that continuous electrical brain stimulation itself induced the development of the brain glioma.

406 Article Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines. 2016

Fujimori, Koki / Tezuka, Toshiki / Ishiura, Hiroyuki / Mitsui, Jun / Doi, Koichiro / Yoshimura, Jun / Tada, Hirobumi / Matsumoto, Takuya / Isoda, Miho / Hashimoto, Ryota / Hattori, Nubutaka / Takahashi, Takuya / Morishita, Shinichi / Tsuji, Shoji / Akamatsu, Wado / Okano, Hideyuki. ·Department of Physiology, Keio University, School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan. · Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan. · Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-0882, Japan. · Department of Physiology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Kanagawa, 236-0027, Japan. · Department of Integrative Aging Neuroscience, Section of Neuroendocrinology, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan. · Institute for Innovation, Ajinomoto Co., Inc., Kawasaki-ku, Kanagawa, 210-8681, Japan. · Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita-shi, Osaka, 565-0871, Japan. · Department of Psychiatry, Osaka University Graduate School of Medicine, Suita-shi, Osaka, 565-0871, Japan. · Department of Neurology, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo, 113-8431, Japan. · Medical Genome Center, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, 113-8655, Japan. · Department of Physiology, Keio University, School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan. awado@juntendo.ac.jp. · Center for Genomic and Regenerative Medicine, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo, 113-8431, Japan. awado@juntendo.ac.jp. · Department of Physiology, Keio University, School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan. hidokano@a2.keio.jp. ·Mol Brain · Pubmed #27716287.

ABSTRACT: Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs. However, it remains unclear whether patient's LCL-derived iPSCs (LiPSCs) can function as a disease model. Therefore, we generated Parkinson's disease patient-specific LiPSCs and evaluated their utility as tools for modeling neurological diseases. We established iPSCs from two LCL clones, which were derived from a healthy donor and a patient carrying PARK2 mutations, by using existing non-integrating episomal protocols. Whole genome sequencing (WGS) and comparative genomic hybridization (CGH) analyses showed that the appearance of somatic variations in the genomes of the iPSCs did not vary substantially according to the original cell types (LCLs, T-cells and fibroblasts). Furthermore, LiPSCs could be differentiated into functional neurons by using the direct neurosphere conversion method (dNS method), and they showed several Parkinson's disease phenotypes that were similar to those of DF-iPSCs. These data indicate that the global LCL repositories can be used as a resource for generating iPSCs and disease models. Thus, LCLs are the powerful tools for generating iPSCs and modeling neurological diseases.

407 Article Novel genetic loci underlying human intracranial volume identified through genome-wide association. 2016

Adams, Hieab H H / Hibar, Derrek P / Chouraki, Vincent / Stein, Jason L / Nyquist, Paul A / Rentería, Miguel E / Trompet, Stella / Arias-Vasquez, Alejandro / Seshadri, Sudha / Desrivières, Sylvane / Beecham, Ashley H / Jahanshad, Neda / Wittfeld, Katharina / Van der Lee, Sven J / Abramovic, Lucija / Alhusaini, Saud / Amin, Najaf / Andersson, Micael / Arfanakis, Konstantinos / Aribisala, Benjamin S / Armstrong, Nicola J / Athanasiu, Lavinia / Axelsson, Tomas / Beiser, Alexa / Bernard, Manon / Bis, Joshua C / Blanken, Laura M E / Blanton, Susan H / Bohlken, Marc M / Boks, Marco P / Bralten, Janita / Brickman, Adam M / Carmichael, Owen / Chakravarty, M Mallar / Chauhan, Ganesh / Chen, Qiang / Ching, Christopher R K / Cuellar-Partida, Gabriel / Braber, Anouk Den / Doan, Nhat Trung / Ehrlich, Stefan / Filippi, Irina / Ge, Tian / Giddaluru, Sudheer / Goldman, Aaron L / Gottesman, Rebecca F / Greven, Corina U / Grimm, Oliver / Griswold, Michael E / Guadalupe, Tulio / Hass, Johanna / Haukvik, Unn K / Hilal, Saima / Hofer, Edith / Hoehn, David / Holmes, Avram J / Hoogman, Martine / Janowitz, Deborah / Jia, Tianye / Kasperaviciute, Dalia / Kim, Sungeun / Klein, Marieke / Kraemer, Bernd / Lee, Phil H / Liao, Jiemin / Liewald, David C M / Lopez, Lorna M / Luciano, Michelle / Macare, Christine / Marquand, Andre / Matarin, Mar / Mather, Karen A / Mattheisen, Manuel / Mazoyer, Bernard / McKay, David R / McWhirter, Rebekah / Milaneschi, Yuri / Mirza-Schreiber, Nazanin / Muetzel, Ryan L / Maniega, Susana Muñoz / Nho, Kwangsik / Nugent, Allison C / Loohuis, Loes M Olde / Oosterlaan, Jaap / Papmeyer, Martina / Pappa, Irene / Pirpamer, Lukas / Pudas, Sara / Pütz, Benno / Rajan, Kumar B / Ramasamy, Adaikalavan / Richards, Jennifer S / Risacher, Shannon L / Roiz-Santiañez, Roberto / Rommelse, Nanda / Rose, Emma J / Royle, Natalie A / Rundek, Tatjana / Sämann, Philipp G / Satizabal, Claudia L / Schmaal, Lianne / Schork, Andrew J / Shen, Li / Shin, Jean / Shumskaya, Elena / Smith, Albert V / Sprooten, Emma / Strike, Lachlan T / Teumer, Alexander / Thomson, Russell / Tordesillas-Gutierrez, Diana / Toro, Roberto / Trabzuni, Daniah / Vaidya, Dhananjay / Van der Grond, Jeroen / Van der Meer, Dennis / Van Donkelaar, Marjolein M J / Van Eijk, Kristel R / Van Erp, Theo G M / Van Rooij, Daan / Walton, Esther / Westlye, Lars T / Whelan, Christopher D / Windham, Beverly G / Winkler, Anderson M / Woldehawariat, Girma / Wolf, Christiane / Wolfers, Thomas / Xu, Bing / Yanek, Lisa R / Yang, Jingyun / Zijdenbos, Alex / Zwiers, Marcel P / Agartz, Ingrid / Aggarwal, Neelum T / Almasy, Laura / Ames, David / Amouyel, Philippe / Andreassen, Ole A / Arepalli, Sampath / Assareh, Amelia A / Barral, Sandra / Bastin, Mark E / Becker, Diane M / Becker, James T / Bennett, David A / Blangero, John / van Bokhoven, Hans / Boomsma, Dorret I / Brodaty, Henry / Brouwer, Rachel M / Brunner, Han G / Buckner, Randy L / Buitelaar, Jan K / Bulayeva, Kazima B / Cahn, Wiepke / Calhoun, Vince D / Cannon, Dara M / Cavalleri, Gianpiero L / Chen, Christopher / Cheng, Ching-Yu / Cichon, Sven / Cookson, Mark R / Corvin, Aiden / Crespo-Facorro, Benedicto / Curran, Joanne E / Czisch, Michael / Dale, Anders M / Davies, Gareth E / De Geus, Eco J C / De Jager, Philip L / de Zubicaray, Greig I / Delanty, Norman / Depondt, Chantal / DeStefano, Anita L / Dillman, Allissa / Djurovic, Srdjan / Donohoe, Gary / Drevets, Wayne C / Duggirala, Ravi / Dyer, Thomas D / Erk, Susanne / Espeseth, Thomas / Evans, Denis A / Fedko, Iryna O / Fernández, Guillén / Ferrucci, Luigi / Fisher, Simon E / Fleischman, Debra A / Ford, Ian / Foroud, Tatiana M / Fox, Peter T / Francks, Clyde / Fukunaga, Masaki / Gibbs, J Raphael / Glahn, David C / Gollub, Randy L / Göring, Harald H H / Grabe, Hans J / Green, Robert C / Gruber, Oliver / Gudnason, Vilmundur / Guelfi, Sebastian / Hansell, Narelle K / Hardy, John / Hartman, Catharina A / Hashimoto, Ryota / Hegenscheid, Katrin / Heinz, Andreas / Le Hellard, Stephanie / Hernandez, Dena G / Heslenfeld, Dirk J / Ho, Beng-Choon / Hoekstra, Pieter J / Hoffmann, Wolfgang / Hofman, Albert / Holsboer, Florian / Homuth, Georg / Hosten, Norbert / Hottenga, Jouke-Jan / Hulshoff Pol, Hilleke E / Ikeda, Masashi / Ikram, M Kamran / Jack, Clifford R / Jenkinson, Mark / Johnson, Robert / Jönsson, Erik G / Jukema, J Wouter / Kahn, René S / Kanai, Ryota / Kloszewska, Iwona / Knopman, David S / Kochunov, Peter / Kwok, John B / Lawrie, Stephen M / Lemaître, Hervé / Liu, Xinmin / Longo, Dan L / Longstreth, W T / Lopez, Oscar L / Lovestone, Simon / Martinez, Oliver / Martinot, Jean-Luc / Mattay, Venkata S / McDonald, Colm / McIntosh, Andrew M / McMahon, Katie L / McMahon, Francis J / Mecocci, Patrizia / Melle, Ingrid / Meyer-Lindenberg, Andreas / Mohnke, Sebastian / Montgomery, Grant W / Morris, Derek W / Mosley, Thomas H / Mühleisen, Thomas W / Müller-Myhsok, Bertram / Nalls, Michael A / Nauck, Matthias / Nichols, Thomas E / Niessen, Wiro J / Nöthen, Markus M / Nyberg, Lars / Ohi, Kazutaka / Olvera, Rene L / Ophoff, Roel A / Pandolfo, Massimo / Paus, Tomas / Pausova, Zdenka / Penninx, Brenda W J H / Pike, G Bruce / Potkin, Steven G / Psaty, Bruce M / Reppermund, Simone / Rietschel, Marcella / Roffman, Joshua L / Romanczuk-Seiferth, Nina / Rotter, Jerome I / Ryten, Mina / Sacco, Ralph L / Sachdev, Perminder S / Saykin, Andrew J / Schmidt, Reinhold / Schofield, Peter R / Sigurdsson, Sigurdur / Simmons, Andy / Singleton, Andrew / Sisodiya, Sanjay M / Smith, Colin / Smoller, Jordan W / Soininen, Hilkka / Srikanth, Velandai / Steen, Vidar M / Stott, David J / Sussmann, Jessika E / Thalamuthu, Anbupalam / Tiemeier, Henning / Toga, Arthur W / Traynor, Bryan J / Troncoso, Juan / Turner, Jessica A / Tzourio, Christophe / Uitterlinden, Andre G / Hernández, Maria C Valdés / Van der Brug, Marcel / Van der Lugt, Aad / Van der Wee, Nic J A / Van Duijn, Cornelia M / Van Haren, Neeltje E M / Van T Ent, Dennis / Van Tol, Marie-Jose / Vardarajan, Badri N / Veltman, Dick J / Vernooij, Meike W / Völzke, Henry / Walter, Henrik / Wardlaw, Joanna M / Wassink, Thomas H / Weale, Michael E / Weinberger, Daniel R / Weiner, Michael W / Wen, Wei / Westman, Eric / White, Tonya / Wong, Tien Y / Wright, Clinton B / Zielke, H Ronald / Zonderman, Alan B / Deary, Ian J / DeCarli, Charles / Schmidt, Helena / Martin, Nicholas G / De Craen, Anton J M / Wright, Margaret J / Launer, Lenore J / Schumann, Gunter / Fornage, Myriam / Franke, Barbara / Debette, Stéphanie / Medland, Sarah E / Ikram, M Arfan / Thompson, Paul M / and others. ·Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. · Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands. · Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, USA. · Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. · Lille University, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of aging-related diseases, Lille, France. · Framingham Heart Study, Framingham, Massachusetts, USA. · Department of Genetics and UNC Neuroscience Center, University of North Carolina (UNC), Chapel Hill, North Carolina, USA. · Department of Neurology, Department of Anesthesia/Critical Care Medicine, Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA. · QIMR Berghofer Medical Research Institute, Brisbane, Australia. · Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands. · Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. · MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida, USA. · John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA. · German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald, Germany. · Department of Psychiatry, University Medicine Greifswald, Greifswald, Germany. · Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht, the Netherlands. · Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. · The Royal College of Surgeons in Ireland, Dublin 2, Ireland. · Department of Integrative Medical Biology and Umeå center for Functional Brain Imaging, Umeå University, Umeå, Sweden. · Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA. · Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, Illinois, USA. · Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UK. · Department of Computer Science, Lagos State University, Lagos, Nigeria. · Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK. · Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia. · Mathematics and Statistics, Murdoch University, Perth, Australia. · NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. · Hospital for Sick Children, University of Toronto, Toronto, Canada. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA. · Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. · G.H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. · Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada. · Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada. · INSERM Unit U1219, University of Bordeaux, France. · Lieber Institute for Brain Development, Baltimore, Maryland, USA. · Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California, USA. · Biological Psychology, Neuroscience Campus Amsterdam, Vrije Universiteit University and Vrije Universiteit Medical Center, Amsterdam, the Netherlands. · Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Germany. · Department of Psychiatry, Massachusetts General Hospital, Boston, Masschusetts, USA. · Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, North Carolina, USA. · NSERM Unit 1000 ″Neuroimaging and Psychiatry″, University Paris Sud, University Paris Descartes, Paris, France. · Maison de Solenn, Adolescent Psychopathology and Medicine Department, APHP Hospital Cochin, Paris, France. · Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. · NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Norway. · Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands. · King's College London, Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychology, Psychiatry and Neurosciene, London, UK. · Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany. · Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, Mississippi, USA. · Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands. · International Max Planck Research School for Language Sciences, Nijmegen, the Netherlands. · Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden, Germany. · Department of Research and Development, Diakonhjemmet Hospital, Oslo, Norway. · Department of Pharmacology, National University of Singapore, Singapore. · Memory Aging and Cognition Centre (MACC), National University Health System, Singapore. · Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Austria, Graz, Austria. · Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Austria, Graz, Austria. · Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany. · Department of Psychology, Yale University, New Haven, Connecticut, USA. · UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, Bucks, UK. · Department of Medicine, Imperial College London, London, UK. · Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany. · Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Lexington, Massachusetts, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh, UK. · Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, The Netherlands. · Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. · Department of Biomedicine, Aarhus University, Aarhus, Denmark. · The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark. · Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. · UMR5296 University of Bordeaux, CNRS, CEA, Bordeaux, France. · Department of Psychiatry, Yale University, New Haven, Connecticut, USA. · Olin Neuropsychiatric Research Center, Hartford, Connecticut, USA. · Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. · Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands. · Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA. · Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA. · Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, the Netherlands. · Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK. · Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern, Switzerland. · School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois, USA. · Department of Medical and Molecular Genetics, King's College London, London, UK. · The Jenner Institute Laboratories, University of Oxford, Oxford, UK. · Department of Medicine and Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain. · CIBERSAM (Centro Investigación Biomédica en Red Salud Mental), Santander, Spain. · Psychosis Research Group, Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin. · Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. · Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida, USA. · Department of Epidemiology and Public Health Sciences, University of Miami, Miller School of Medicine, Miami, Florida, USA. · Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia. · Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia. · Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. · Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, USA. · Department of Cognitive Sciences, University of California, San Diego, USA. · Icelandic Heart Association, Kopavogur, Iceland. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Queensland Brain Institute, University of Queensland, Brisbane, Australia. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · School of Computing Engineering and Mathematics, Western Sydney University, Parramatta, Australia. · Neuroimaging Unit,Technological Facilities. Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, Spain. · Institut Pasteur, Paris, France. · Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. · GeneSTAR Research Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Brain Center Rudolf Magnus, Human Neurogenetics Unit, UMC Utrecht, Utrecht, the Netherlands. · Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, California, USA. · NORMENT - KG Jebsen Centre, Department of Psychology, University of Oslo, Oslo, Norway. · Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. · FMRIB Centre, University of Oxford, Oxford, UK. · University of Wuerzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Biospective Inc, Montreal, Quebec, Canada, Montréal, Québec, Canada. · Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden. · South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine Brownsville/Edinburg/San Antonio, Texas, USA. · Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. · National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Australia. · Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia. · Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. · Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Dementia Collaborative Research Centre - Assessment and Better Care, UNSW, Sydney, Australia. · Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA. · Department of Evolution and Genetics, Dagestan State University, Makhachkala, Dagestan, Russia. · The Mind Research Network and LBERI, Albuquerque, New Mexico, USA. · Department of ECE, University of New Mexico, Albuquerque, New Mexico, USA. · Centre for Neuroimaging and Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. · Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany. · Center for Multimodal Imaging and Genetics, University of California, San Diego, California, USA. · Department of Neurosciences, University of California, San Diego, California, USA. · Department of Radiology, University of California, San Diego, California, USA. · Department of Psychiatry, University of California, San Diego, California, USA. · Department of Cognitive Science, University of California, San Diego, California, USA. · Avera Institute for Human Genetics, Sioux Falls, South Dakota, USA. · Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. · Broad Institute, Cambridge, Massachusetts, USA. · Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia. · Neurology Division, Beaumont Hospital, Dublin, 9, Ireland. · Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. · Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. · Cognitive Genetics and Cognitive Therapy Group, Neuroimaging, Cognition and Genomics Centre (NICOG) and NCBES Galway Neuroscience Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. · Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 8, Ireland. · Janssen Research and Development, LLC, Titusville, New Jersey, USA. · Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin, Germany. · Intramural Research Program of the National Institute on Aging, Baltimore, Maryland, USA. · Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK. · Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA. · University of Texas Health Science Center, San Antonio, Texas, USA. · Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan. · Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan. · Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan. · Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. · German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. · Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands. · Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA. · HMNC Brain Health, Munich, Germany. · Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. · Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. · Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. · NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland, USA. · School of Psychology, University of Sussex, Brighton, UK. · Institute of Cognitive Neuroscience, University College London, London, UK. · Department of Neuroinformatics, Araya Brain Imaging, Tokyo, Japan. · Medical University of Lodz, Lodz, Poland. · Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA. · Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Neuroscience Research Australia, Sydney, Australia. · School of Medical Sciences, UNSW, Sydney, Australia. · Columbia University Medical Center, New York, New York, USA. · Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. · Department of Neurology, University of Washington, Seattle, Washington, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Department of Psychiatry, University of Oxford, Oxford, UK. · NIHR Dementia Biomedical Research Unit, King's College London, London, UK. · Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, California, USA. (and more) ·Nat Neurosci · Pubmed #27694991.

ABSTRACT: Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ

408 Article Adjunctive preladenant: A placebo-controlled, dose-finding study in Japanese patients with Parkinson's disease. 2016

Hattori, Nobutaka / Kikuchi, Masashi / Adachi, Noriaki / Hewitt, David / Huyck, Susan / Saito, Tadayuki. ·Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp. · Japan Development, MSD K.K., Tokyo, Japan. · Merck & Co., Inc., Kenilworth, NJ, USA. ·Parkinsonism Relat Disord · Pubmed #27632893.

ABSTRACT: BACKGROUND: Preladenant, an adenosine 2A antagonist, reduced daily OFF time when administered as adjunctive treatment in a previous phase 2 trial in non-Japanese Parkinson's disease (PD) patients on stable doses of levodopa. This study aimed to evaluate preladenant as adjunctive therapy in Japanese patients with PD. METHODS: In this randomized, placebo-controlled, double-blind, 12-week, dose-ranging, phase 2 study, Japanese patients with moderate to severe PD on a stable regimen of levodopa were randomly assigned 1:1:1:1 to preladenant 2 mg, 5 mg, or 10 mg BID or placebo. The primary efficacy end point was change from baseline to week 12 in mean OFF time, recorded using a PD diary. Safety and tolerability were also assessed. RESULTS: In total, 111 patients were randomly assigned to receive preladenant 2 mg, and 113 each received preladenant 5 mg, 10 mg, or placebo. In contrast to previous data, preladenant in this study did not demonstrate statistically significant efficacy; the primary outcome was -0.7 h (P = 0.0564), -0.5 h (P = 0.1844), and -0.3 h (P = 0.3386), respectively, for preladenant 2 mg, 5 mg, and 10 mg BID versus placebo. Overall, preladenant was well tolerated, and the frequency of adverse events appeared to be dose related. CONCLUSIONS: In this phase 2 study, preladenant used as adjunctive therapy in PD patients on stable doses of levodopa did not reduce mean OFF time; treatment was well tolerated at doses between 2 and 10 mg BID.

409 Article Re-emergent tremor in a patient with Parkinson's disease. 2016

Noda, Kazuyuki / Hattori, Nobutaka / Okuma, Yasuyuki. ·Department of Neurology, Juntendo Shizuoka Hospital, Izunokuni, Shizuoka, Japan. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. ·BMJ Case Rep · Pubmed #27495177.

ABSTRACT: -- No abstract --

410 Article Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril. 2016

Kim, Changyoun / Lv, Guohua / Lee, Jun Sung / Jung, Byung Chul / Masuda-Suzukake, Masami / Hong, Chul-Suk / Valera, Elvira / Lee, He-Jin / Paik, Seung R / Hasegawa, Masato / Masliah, Eliezer / Eliezer, David / Lee, Seung-Jae. ·Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea. · Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA. · Department of Biochemistry, Weill Cornell Medical College, NY, USA. · Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju, Korea. · Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. · School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, Korea. · Department of Anatomy, School of Medicine, Konkuk University, Seoul, Korea. ·Sci Rep · Pubmed #27488222.

ABSTRACT: A single amyloidogenic protein is implicated in multiple neurological diseases and capable of generating a number of aggregate "strains" with distinct structures. Among the amyloidogenic proteins, α-synuclein generates multiple patterns of proteinopathies in a group of diseases, such as Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, the link between specific conformations and distinct pathologies, the key concept of the strain hypothesis, remains elusive. Here we show that in the presence of bacterial endotoxin, lipopolysaccharide (LPS), α-synuclein generated a self-renewable, structurally distinct fibril strain that consistently induced specific patterns of synucleinopathies in mice. These results suggest that amyloid fibrils with self-renewable structures cause distinct types of proteinopathies despite the identical primary structure and that exposure to exogenous pathogens may contribute to the diversity of synucleinopathies.

411 Article Oxidation and interaction of DJ-1 with 20S proteasome in the erythrocytes of early stage Parkinson's disease patients. 2016

Saito, Yoshiro / Akazawa-Ogawa, Yoko / Matsumura, Akihiro / Saigoh, Kazumasa / Itoh, Sayoko / Sutou, Kenta / Kobayashi, Mayuka / Mita, Yuichiro / Shichiri, Mototada / Hisahara, Shin / Hara, Yasuo / Fujimura, Harutoshi / Takamatsu, Hiroyuki / Hagihara, Yoshihisa / Yoshida, Yasukazu / Hamakubo, Takao / Kusunoki, Susumu / Shimohama, Shun / Noguchi, Noriko. ·Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan. · National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan. · Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan. · Department of Neurology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan. · Hamamatsu Pharma Research Inc., Hamamatsu 431-2103, Japan. · Hara Clinic, Ikeda, Osaka 563-0025, Japan. · Department of Neurology, National Hospital Organization Toneyama National Hospital, Toyonaka, Osaka 560-8552, Japan. · Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-0041, Japan. ·Sci Rep · Pubmed #27470541.

ABSTRACT: Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress. Here, using specific antibodies against Cys-106-oxidized DJ-1 (oxDJ-1), it was found that the levels of oxDJ-1 in the erythrocytes of unmedicated PD patients (n = 88) were higher than in those of medicated PD patients (n = 62) and healthy control subjects (n = 33). Elevated oxDJ-1 levels were also observed in a non-human primate PD model. Biochemical analysis of oxDJ-1 in erythrocyte lysates showed that oxDJ-1 formed dimer and polymer forms, and that the latter interacts with 20S proteasome. These results clearly indicate a biochemical alteration in the blood of PD patients, which could be utilized as an early diagnosis marker for PD.

412 Article Relation between Resting State Front-Parietal EEG Coherence and Executive Function in Parkinson's Disease. 2016

Teramoto, Hiroko / Morita, Akihiko / Ninomiya, Satoko / Akimoto, Takayoshi / Shiota, Hiroshi / Kamei, Satoshi. ·Division of Neurology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan. ·Biomed Res Int · Pubmed #27433473.

ABSTRACT: Objective. To assess the relation between executive dysfunction (ED) in Parkinson's disease (PD) and resting state functional connectivity evaluated using electroencephalography (EEG) coherence. Methods. Sixty-eight nondemented sporadic PD patients were assessed using the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to evaluate executive function. EEG coherence in the left frontoparietal electrode pair (F3-P3) and the right frontoparietal electrode pair (F4-P4) was analyzed in the alpha and theta range. The BADS scores were compared across the coherence groups, and the multiple logistic regression analysis was performed to assess the contribution of confounders. Results. The standardized BADS score was significantly lower in the low F3-P3 coherence group in the alpha range (Mann-Whitney U test, p = 0.032), though there was no difference between F4-P4 coherence group in the alpha range, F3-P3, and F4-P4 coherence groups in the theta range and the standardized BADS score. The multiple logistic regression analysis revealed the significant relation between the F3-P3 coherence group in alpha range and age-controlled standardized BADS score (p = 0.039, 95% CI = 1.002-1.062). Conclusion. The decrease in resting state functional connectivity between the frontal and parietal cortices especially in the left side is related to ED in PD.

413 Article Biochemical and clinical effects of Whey protein supplementation in Parkinson's disease: A pilot study. 2016

Tosukhowong, Piyaratana / Boonla, Chanchai / Dissayabutra, Thasinas / Kaewwilai, Lalita / Muensri, Sasipa / Chotipanich, Chanisa / Joutsa, Juho / Rinne, Juha / Bhidayasiri, Roongroj. ·Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. · Chulalongkorn Center of Excellence for Parkinson's Disease and Related Disorders, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand. · National Cyclotron and PET Center, Chulabhorn Hospital, Bangkok, Thailand. · Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland. · Chulalongkorn Center of Excellence for Parkinson's Disease and Related Disorders, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand; Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan. ·J Neurol Sci · Pubmed #27423583.

ABSTRACT: BACKGROUND: Parkinson's disease (PD) is an oxidative stress-mediated degenerative disorder. Elevated plasma homocysteine (Hcy) is frequently found in the levodopa-treated PD patients, is associated with disease progression and is a marker of oxidative stress. Whey protein is a rich source of cysteine, and branched-chain amino acids (BCAA). It has been shown that supplementation with Whey protein increases glutathione synthesis and muscle strength. OBJECTIVES AND METHODS: In this study, we conducted a placebo-controlled, double-blind study (NCT01662414) to investigate the effects of undenatured Whey protein isolate supplementation for 6months on plasma glutathione, plasma amino acids, and plasma Hcy in PD patients. Clinical outcome assessments included the unified Parkinson's disease rating scale (UPDRS) and striatal L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) uptake were determined before and after supplementation. 15 patients received Whey protein, and 17 received Soy protein, served as a control group. RESULTS: Significant increases in plasma concentration of reduced glutathione and the ratio of reduced to oxidized glutathione were found in the Whey-supplemented patients but not in a control group. This was associated with a significant decrease of plasma levels of Hcy. The plasma levels of total glutathione were not significantly changed in either group. Plasma BCAA and essential amino acids (EAA) were significantly increased in the Whey-supplemented group only. The UPDRS and striatal FDOPA uptake in PD patients were not significantly ameliorated in either group. However, significant negative correlation was observed between the UPDRS and plasma BCAA and EAA in the pre-supplemented PD patients. CONCLUSION: This study is the first to report that Whey protein supplementation significantly increases plasma reduced glutathione, the reduced to oxidized glutathione ratio, BCAAs and EAAs in patients with PD, together with a concomitant significant reduction of plasma Hcy. However, there were no significant changes in clinical outcomes. Long-term, large randomized clinical studies are needed to explore the benefits of Whey protein supplementation in the management of PD patients.

414 Article Predictors of postprandial hypotension in elderly patients with de novo Parkinson's disease. 2016

Umehara, Tadashi / Nakahara, Atsuo / Matsuno, Hiromasa / Toyoda, Chizuko / Oka, Hisayoshi. ·Department of Neurology, Daisan Hospital, The Jikei University School of Medicine, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan. tumety@jikei.ac.jp. · Department of Neurology, Daisan Hospital, The Jikei University School of Medicine, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan. · Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan. · Department of Neurology, Daisan Hospital, The Jikei University School of Medicine, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan. h.oka@jikei.ac.jp. ·J Neural Transm (Vienna) · Pubmed #27393383.

ABSTRACT: Postprandial hypotension is one of the most important autonomic disorders in Parkinson's disease. However, its predictors remain unclear. We investigated which variable(s) predict the presence of postprandial hypotension in elderly patients with Parkinson's disease. The subjects were 64 patients with de novo Parkinson's disease who were 70 years or older. Postprandial hypotension was evaluated on a 75-g oral glucose tolerance test. Olfactory function, constipation, cardiac sympathetic or parasympathetic denervation, orthostatic intolerance on head-up tilt table testing, and other baseline characteristics were evaluated. The results showed the presence of postprandial hypotension was associated with severe dysosmia, constipation, orthostatic hypotension (a decrease in systolic blood pressure ≥30 mmHg) and preprandial hypertension at rest. On multiple logistic regression analyses adjusted for age, sex, symptom duration, disease severity, and motor subtype, the odds ratio was 4.02 for severe dysosmia (p = 0.027), 9.99 for constipation (p = 0.006), 6.42 for orthostatic hypotension with alternative definition (p = 0.004) and 7.90 for preprandial hypertension at rest (p = 0.001). Each multiple logistic regression analysis revealed that female sex was also a risk factor for postprandial hypotension. The variables with the highest sensitivity and specificity for postprandial hypotension were constipation (89.6 %) and preprandial hypertension at rest or orthostatic hypotension with alternative definition (both 77.1 %), respectively. Our results suggest that these variables predict the presence of postprandial hypotension in elderly patients with Parkinson's disease, suggesting that postprandial hypotension shares etiologic factors with these potential predictors.

415 Article The Effect of Fragmented Pathogenic α-Synuclein Seeds on Prion-like Propagation. 2016

Tarutani, Airi / Suzuki, Genjiro / Shimozawa, Aki / Nonaka, Takashi / Akiyama, Haruhiko / Hisanaga, Shin-Ichi / Hasegawa, Masato. ·From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan and the Department of Biological Science, Tokyo Metropolitan University, Tokyo 192-0397, Japan. · From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan and. · the Department of Biological Science, Tokyo Metropolitan University, Tokyo 192-0397, Japan. · From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan and hasegawa-ms@igakuken.or.jp. ·J Biol Chem · Pubmed #27382062.

ABSTRACT: Aggregates of abnormal proteins are widely observed in neuronal and glial cells of patients with various neurodegenerative diseases, and it has been proposed that prion-like behavior of these proteins can account for not only the onset but also the progression of these diseases. However, it is not yet clear which abnormal protein structures function most efficiently as seeds for prion-like propagation. In this study, we aimed to identify the most pathogenic species of α-synuclein (α-syn), the main component of the Lewy bodies and Lewy neurites that are observed in α-synucleinopathies. We prepared various forms of α-syn protein and examined their seeding properties in vitro in cells and in mouse experimental models. We also characterized these α-syn species by means of electron microscopy and thioflavin fluorescence assays and found that fragmented β sheet-rich fibrous structures of α-syn with a length of 50 nm or less are the most efficient promoters of accumulation of phosphorylated α-syn, which is the hallmark of α-synucleinopathies. These results indicate that fragmented amyloid-like aggregates of short α-syn fibrils are the key pathogenic seeds that trigger prion-like conversion.

416 Article Treatment of Mild Camptocormia with Selegiline in Patients with Parkinson's Disease. 2016

Yoritaka, Asako / Mori, Hideo / Hattori, Nobutaka. ·Department of Neurology, Juntendo University Koshigaya Hospital, Saitama, Japan. ·Eur Neurol · Pubmed #27351804.

ABSTRACT: BACKGROUND: Camptocormia in Parkinson's disease (PD) is unresponsive to various therapies and induced difficulties in their day-to-day life. OBJECTIVE: This study, an open trial, was aimed at assessing the efficacy of selegiline in the treatment of mild camptocormia in PD patients. METHODS: Participants were administered 5 mg of selegiline for the first 8 weeks and 7.5 mg for the second 8 weeks. RESULTS: As primary endpoints, the degree of thoracolumbar anteflexion decreased from 23.2° (mean) (11.8° (SD)) at baseline to 18.3° (7.1°) at 16 weeks, and the area of postural sway measured using a Gravicorder increased. However, the differences were not significant. Thoracolumbar anteflexion improved in 60% of the participants. CONCLUSIONS: In this study, 60% of the participants showed an improvement in anteflexion of the thoracolumbar spine with selegiline, but the change in the degree of anteflexion was 5°, which was not statistically significant. Participants with significant improvement in thoracolumbar anteflexion had an increased postural sway. This change was induced by a decrease in truncal muscle tonus or change in the center of gravity. This study combined the study of anteflexion and stability, and provides information on the treatment of short-term or mild camptocormia.

417 Article Unexpected mitochondrial matrix localization of Parkinson's disease-related DJ-1 mutants but not wild-type DJ-1. 2016

Kojima, Waka / Kujuro, Yuki / Okatsu, Kei / Bruno, Queliconi / Koyano, Fumika / Kimura, Mayumi / Yamano, Koji / Tanaka, Keiji / Matsuda, Noriyuki. ·Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan. · Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan. · Tachikawa Hospital, 4-2-22 Nishikimachi, Tachikawa, Tokyo, 190-8531, Japan. · Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. · Structural Biology Laboratory, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo, 113-0032, Japan. · Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan. · PRESTO, JST, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. ·Genes Cells · Pubmed #27270837.

ABSTRACT: DJ-1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ-1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ-1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ-1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ-1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ-1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ-1 possesses neither an amino-terminal alpha-helix nor a predictable matrix-targeting signal, and a post-translocation processing-derived molecular weight change is not observed. In fact, wild-type DJ-1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ-1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ-1 mutants.

418 Article Neuroprotective and anti-inflammatory effects of morin in a murine model of Parkinson's disease. 2016

Lee, Kyung Moon / Lee, Yujeong / Chun, Hye Jeong / Kim, Ah Hyun / Kim, Ju Yeon / Lee, Joo Yeon / Ishigami, Akihito / Lee, Jaewon. ·Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea. · Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. ·J Neurosci Res · Pubmed #27265894.

ABSTRACT: Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP-induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1-methyl-4-phenylpyridine (MPP(+) )-mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP(+) -induced astroglial activation and nuclear translocation of nuclear factor-κB in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. © 2016 Wiley Periodicals, Inc.

419 Article Effect of Interpersonal Interaction on Festinating Gait Rehabilitation in Patients with Parkinson's Disease. 2016

Uchitomi, Hirotaka / Ogawa, Ken-Ichiro / Orimo, Satoshi / Wada, Yoshiaki / Miyake, Yoshihiro. ·Department of Computational Intelligence and Systems Science, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan. · Department of Neurology, Kanto Central Hospital, Setagaya, Tokyo, Japan. · Department of Rehabilitation, Nissan Tamagawa Hospital, Setagaya, Tokyo, Japan. ·PLoS One · Pubmed #27253376.

ABSTRACT: TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000012591.

420 Article α-Synuclein Fibrils Exhibit Gain of Toxic Function, Promoting Tau Aggregation and Inhibiting Microtubule Assembly. 2016

Oikawa, Takayuki / Nonaka, Takashi / Terada, Makoto / Tamaoka, Akira / Hisanaga, Shin-Ichi / Hasegawa, Masato. ·From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, the Department of Biological Science, Tokyo Metropolitan University, Tokyo 192-0397, and. · From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506. · From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, the Department of Neurology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi 305-8576, Japan. · the Department of Neurology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi 305-8576, Japan. · the Department of Biological Science, Tokyo Metropolitan University, Tokyo 192-0397, and. · From the Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, hasegawa-ms@igakuken.or.jp. ·J Biol Chem · Pubmed #27226637.

ABSTRACT: α-Synuclein is the major component of Lewy bodies and Lewy neurites in Parkinson disease and dementia with Lewy bodies and of glial cytoplasmic inclusions in multiple system atrophy. It has been suggested that α-synuclein fibrils or intermediate protofibrils in the process of fibril formation may have a toxic effect on neuronal cells. In this study, we investigated the ability of soluble monomeric α-synuclein to promote microtubule assembly and the effects of conformational changes of α-synuclein on Tau-promoted microtubule assembly. In marked contrast to previous findings, monomeric α-synuclein had no effect on microtubule polymerization. However, both α-synuclein fibrils and protofibrils inhibited Tau-promoted microtubule assembly. The inhibitory effect of α-synuclein fibrils was greater than that of the protofibrils. Dot blot overlay assay and spin-down techniques revealed that α-synuclein fibrils bind to Tau and inhibit microtubule assembly by depleting the Tau available for microtubule polymerization. Using various deletion mutants of α-synuclein and Tau, the acidic C-terminal region of α-synuclein and the basic central region of Tau were identified as regions involved in the binding. Furthermore, introduction of α-synuclein fibrils into cultured cells overexpressing Tau protein induced Tau aggregation. These results raise the possibility that α-synuclein fibrils interact with Tau, inhibit its function to stabilize microtubules, and also promote Tau aggregation, leading to dysfunction of neuronal cells.

421 Article A Japanese multicenter survey characterizing pain in Parkinson's disease. 2016

Kubo, Shin-Ichiro / Hamada, Shinsuke / Maeda, Tetsuya / Uchiyama, Tsuyoshi / Hashimoto, Masaya / Nomoto, Nobuatsu / Kano, Osamu / Takahashi, Tatsuya / Terashi, Hiroo / Takahashi, Tetsuya / Hatano, Taku / Hasegawa, Takafumi / Baba, Yasuhiko / Sengoku, Renpei / Watanabe, Hirohisa / Kadowaki, Taro / Inoue, Manabu / Kaneko, Satoshi / Shimura, Hideki / Nagayama, Hiroshi. ·Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: skubo@juntendo.ac.jp. · Department of Neurology, Hokuyukai Neurological Hospital, 2-4-30 Nijyuyonken-nijo, Nishi-ku, Sapporo 063-0802, Japan. Electronic address: s-hamada@hokuyukai-neurological-hosp.jp. · Department of Neurology and Movement Disorder Research, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubotamachi, Akita 010-0874, Japan. Electronic address: maeda@akita-noken.go.jp. · Department of Neurology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu 430-8558, Japan. Electronic address: tuchiyama@sis.seirei.or.jp. · Department of Neurology, The Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan. Electronic address: hsmtneurology@gmail.com. · Division of Neurology, Department of Internal Medicine, Toho University Ohashi Medical Center, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan. Electronic address: d221001@yahoo.co.jp. · Division of Neurology, Department of Internal Medicine, Toho University Omori Medical Center, 6-11-1 Omorinishi, Ota-ku, Tokyo 143-8541, Japan. Electronic address: osamukano@aol.com. · Department of Neurology, National Hospital Organization Yokohama Medical Center, 3-60-2 Harajuku, Totsuka-ku, Yokohama 245-8575, Japan. Electronic address: tkhsh@yokohama-cu.ac.jp. · Department of Neurology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: terashi@tokyo-med.ac.jp. · Department of Clinical Neuroscience and Therapeutics, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address: tetakaha@mac.com. · Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: thatano@juntendo.ac.jp. · Division of Neurology, Department of Neuroscience & Sensory Organs, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: thasegawa@med.tohoku.ac.jp. · Department of Neurology, Houei Clinic, 1609 Shimonagaecho, Miyakonojo-shi, Miyazaki 885-0061, Japan. Electronic address: yasubaba@tokai-u.jp. · Department of Neurology, The Jikei University School of Medicine, 3-19-18 Nishishinbashi, Minato-ku, Tokyo 105-8471, Japan. Electronic address: renpeis@gmail.com. · Brain and Mind Research Center, Nagoya Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: nabe@med.nagoya-u.ac.jp. · Department of Neurology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. Electronic address: kdtaro@v101.vaio.ne.jp. · Department of Neurology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227-8501, Japan. Electronic address: gakinoue@med.showa-u.ac.jp. · Department of Neurology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan. Electronic address: kanekosa@takii.kmu.ac.jp. · Department of Neurology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Japan. Electronic address: miurashimura@yahoo.co.jp. · Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. Electronic address: nagayama@nms.ac.jp. ·J Neurol Sci · Pubmed #27206899.

ABSTRACT: BACKGROUND: Pain is a frequent, troublesome symptom of PD but is under-recognized and poorly understood. AIM: We characterized pain prevalence, severity, and location in PD, to better understand its pathophysiology and improve diagnosis and treatment. SUBJECTS AND METHODS: A cross-sectional controlled study was conducted at 19 centers across Japan. A total of 632 subjects with Mini-Mental State Examination scores ≥24 were enrolled, including 324 PD patients and 308 controls. Sex and mean age did not differ between the two groups. Demographic and clinical data were collected. Pain was assessed using questionnaires, the SF-36v2 bodily pain scale, and a body illustration for patients to indicate the location of pain in 45 anatomical areas. RESULTS: Pain prevalence in the PD group was 78.6%, significantly higher than in controls (49.0%), as was its severity. There was no correlation between SF-36v2 score and motor scores, such as Unified Parkinson's Disease Rating Scale III or Hoehn & Yahr scores. Pain distribution was similar between groups, predominantly in the lower back, followed by the gluteal region, lower legs, thighs, posterior neck, and shoulders. CONCLUSION: Pain is a significant problem in the Japanese PD population and we discuss its pathophysiology.

422 Article NADPH oxidases promote apoptosis by activating ZNRF1 ubiquitin ligase in neurons treated with an exogenously applied oxidant. 2016

Wakatsuki, Shuji / Araki, Toshiyuki. ·Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira, Tokyo, Japan. ·Commun Integr Biol · Pubmed #27195063.

ABSTRACT: Reactive oxygen species (ROS) play an important role in causing neuronal death in a number of neurological disorders. We recently reported that ROS serve as a signal to activate neuronal apoptosis and axonal degeneration by activating ZNRF1 (zinc- and RING-finger 1), a ubiquitin ligase that targets AKT for proteasomal degradation in neurons. In the present study, we showed that the NADPH oxidase family of molecules is required for ZNRF1 activation by epidermal growth factor receptor (EGFR)-dependent phosphorylation in response to axonal injury. We herein demonstrate that NADPH oxidases promote apoptosis by activating ZNRF1, even in neurons treated with an exogenously applied oxidant. These results suggest an important role for NADPH oxidase in the initiation/promotion of neuronal degeneration by increasing ROS in close proximity to protein machineries, including those for ZNRF1 and EGFR, thereby promoting neuronal degeneration.

423 Article A randomized double-blind multi-center trial of hydrogen water for Parkinson's disease: protocol and baseline characteristics. 2016

Yoritaka, Asako / Abe, Takashi / Ohtsuka, Chigumi / Maeda, Tetsuya / Hirayama, Masaaki / Watanabe, Hirohisa / Saiki, Hidemoto / Oyama, Genko / Fukae, Jiro / Shimo, Yasushi / Hatano, Taku / Kawajiri, Sumihiro / Okuma, Yasuyuki / Machida, Yutaka / Miwa, Hideto / Suzuki, Chikako / Kazama, Asuka / Tomiyama, Masahiko / Kihara, Takeshi / Hirasawa, Motoyuki / Shimura, Hideki / Hattori, Nobutaka. ·Department of Neurology, Juntendo University Koshigaya Hospital, Fukuroyama 560, Koshigayashi, Saitama, 343-0032, Japan. ayori@juntendo.ac.jp. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. ayori@juntendo.ac.jp. · Department of Neurology, Abe Neurological Clinic, Iwate, Japan. · Department of Neurology and Gerontology, Iwate Medical University, Iwate, Japan. · Department of Neurology, Research Institute for Brain and Blood Vessels-Akita Hospital, Akita, Japan. · Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Aichi, Japan. · Brain and Mind Research Center, Nagoya University Graduate School of Medicine, Aichi, Japan. · Department of Neurology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. · Department of Neurology, Fukuoka University, Fukuoka, Japan. · Department of Neurology, Juntendo University Shizuoka Hospital, Shizuoka, Japan. · Department of Neurology, Juntendo University Nerima Hospital, Tokyo, Japan. · Department of Diagnostic Radiology, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. · Nozomi Hospital, Saitama, Japan. · Department of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan. · Department of Neurology, Rakuwakai Otowa Rehabilitation Hospital, Kyoto, Japan. · Department of Neurology, Tokyo Rinkai Hospital, Tokyo, Japan. · Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan. ·BMC Neurol · Pubmed #27176725.

ABSTRACT: BACKGROUND: Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson's Disease Rating Scale (UPDRS) score of Parkinson's disease (PD) patients treated with levodopa. We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial. METHODS: Changes in the total UPDRS scores from baseline to the 8(th), 24(th), 48(th), and 72(nd) weeks, and after the 8(th) week, will be evaluated. The primary endpoint of the efficacy of this treatment in PD is the change in the total UPDRS score from baseline to the 72(nd) week. The changes in UPDRS part II, UPDRS part III, each UPDRS score, PD Questionnaire-39 (PDQ-39), and the modified Hoehn and Yahr stage at these same time-points, as well as the duration until the protocol is finished because additional levodopa is required or until the disease progresses, will also be analyzed. Adverse events and screening laboratory studies will also be examined. Participants in the hydrogen water group will drink 1000 mL/day of H2 water, and those in the placebo water group will drink normal water. One-hundred-and-seventy-eight participants with PD (88 women, 90 men; mean age: 64.2 [SD 9.2] years, total UPDRS: 23.7 [11.8], with levodopa medication: 154 participants, without levodopa medication: 24 participants; daily levodopa dose: 344.1 [202.8] mg, total levodopa equivalent dose: 592.0 [317.6] mg) were enrolled in 14 hospitals and were randomized. DISCUSSION: This study will confirm whether H2 water can improve PD symptoms. TRIAL REGISTRATION: UMIN000010014 (February, 13, 2013).

424 Article Altered expression of Mg(2+) transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells. 2016

Shindo, Yutaka / Yamanaka, Ryu / Suzuki, Koji / Hotta, Kohji / Oka, Kotaro. ·Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan. · Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan. · Department of Bioscience and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan. Electronic address: oka@bio.keio.ac.jp. ·Biochim Biophys Acta · Pubmed #27157538.

ABSTRACT: Mg(2+) is an essential cation to maintain cellular functions, and intracellular Mg(2+) concentration ([Mg(2+)]i) is regulated by Mg(2+) channels and transporters. In our previous study, we demonstrated that MPP(+) elicits Mg(2+) influx across the cell membrane and Mg(2+) mobilization from mitochondria, and the resulting [Mg(2+)]i is an important determinants of the cell viability in MPP(+) model of Parkinson's disease (PD). It indicates that cellular Mg(2+) transport is one of the important factors to determine the progress of PD. However, whether the expression levels of Mg(2+) transport proteins change in the progress of PD has still been obscure. In this study, we estimated the mRNA expression levels of Mg(2+) transport proteins upon the exposure to MPP(+). In thirteen Mg(2+) transport proteins examined, mRNA expression level of SLC41A2 was increased and that of ACDP2, NIPA1 and MMgT2 were decreased. Knockdown of SLC41A2, ACDP2 or NIPA1 accelerated the MPP(+)-induced cell degeneration, and overexpression attenuated it. The decrease in the mRNA expression levels of NIPA1 and MMgT2 were also elicited by rotenone, H2O2 and FCCP, indicating that mitochondrial dysfunction related to this down-regulation. The increase in that of SLC41A2 was induced by an uncoupler, FCCP, as well as MPP(+), suggesting that it is an intrinsic protection mechanism against depolarized mitochondrial membrane potential and/or cellular ATP depletion. Our results shown here indicate that alteration of Mg(2+) transport proteins is implicated in the MPP(+) model of PD, and it affects cell degeneration.

425 Article Dysfunctional counting of mental time in Parkinson's disease. 2016

Honma, Motoyasu / Kuroda, Takeshi / Futamura, Akinori / Shiromaru, Azusa / Kawamura, Mitsuru. ·Department of Neurology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. ·Sci Rep · Pubmed #27146904.

ABSTRACT: Patients with Parkinson's disease (PD) often underestimate time intervals, however it remains unclear why they underestimate rather than overestimate them. The current study examined time underestimation and counting in patients with PD, in relation to dopamine transporter (DaT) located on presynaptic nerve endings in the striatum. Nineteen non-dementia patients with PD and 20 age- and sex-matched healthy controls performed two time estimation tasks to produce or reproduce time intervals with counting in the head, to examine dysfunctional time counting processing. They also performed tapping tasks to measure cycles of counting with 1 s interval with time estimation. Compared to controls, patients underestimated time intervals above 10 s on time production not reproduction tasks, and the underestimation correlated with fast counting on the tapping task. Furthermore, striatal DaT protein levels strongly correlated with underestimation of time intervals. These findings suggest that distortion of time intervals is guided by cumulative output of fast cycle counting and that this is linked with striatal DaT protein deficit.

Back · Next