DOCSLIB.ORG

Dopaminergic Function and Dopamine Transporter Binding Assessed with Positron Emission Tomography in Parkinson Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dopaminergic Function and Dopamine Transporter Binding Assessed with Positron Emission Tomography in Parkinson Disease ORIGINAL CONTRIBUTION Dopaminergic Function and Dopamine Transporter Binding Assessed With Positron Emission Tomography in Parkinson Disease Maria-Joao Ribeiro, MD, PhD; Marie Vidailhet, MD; Christian Loc’h, BS; Corinne Dupel, MD; Jean Paul Nguyen, MD; Michel Ponchant, BS; Fre´de´ric Dolle´, PhD; Marc Peschanski, MD, PhD; Philippe Hantraye, PhD; Pierre Cesaro, MD, PhD; Yves Samson, MD; Philippe Remy, MD, PhD Background: Measuring progression of Parkinson dis- Results: The reduction in 76Br-FE-CBT binding to 43% ease (PD) using positron emission tomography may help of control values was more severe than the reduction in demonstrate the efficacy of neuroprotective treatments. To 18F-dopa uptake (63% of control values) in the putamen date, 18F-dopa has been the gold standard to measure pre- of patients with early PD. No significant difference was synaptic dopaminergic function in PD, but this tracer might found between either tracer’s uptake in the putamen of overestimate the rate of neuronal death in PD because its patients with advanced PD. Motor performance was highly uptake also depends on dopamine turnover rather than ex- correlated to 18F-dopa uptake, whereas correlation to 76Br- clusively on the density of dopaminergic terminals in the FE-CBT binding was weak. striatum. The latter might be assessed using newly devel- oped ligands of the membrane dopamine transporter. Conclusions: Uptake of 18F-dopa may be up-regulated in early PD, suggesting a compensatory increase of do- Objective: To compare the striatal uptakes of 18F-dopa pamine synthesis in surviving dopaminergic terminals. and 76Br-FE-CBT, a dopamine transporter ligand, in pa- Positron emission tomography dopamine transporter tients with PD. ligands and 18F-dopa give complementary information on the presynaptic status of the nigrostriatal dopamin- Patients and Methods: The striatal uptakes of 76Br- ergic system and might be associated to investigate the FE-CBT and 18F-dopa were compared using positron emis- efficacy of neuroprotective treatments in PD. sion tomography in 10 patients with early PD and 8 with advanced PD. Correlation of uptakes with motor perfor- mance was investigated. Arch Neurol. 2002;59:580-586 VALUATING neuroprotec- paminergic synapses was partially com- tive treatments designed to pensated for by increased dopamine me- slow down the progressive tabolism in the surviving terminals (for loss of dopaminergic neu- review see Zigmond et al,9 Hornykie- rons is a crucial step for the wicz,10 and Bezard and Gross11). Thus, Edevelopment of therapeutic strategies in 18F-dopa uptake might overestimate the Parkinson disease (PD). A major draw- number of striatal dopaminergic nerve ter- back faced by previous neuroprotection minals in these patients.12,13 studies in PD was that the potential neu- Ligands that bind to the presynaptic roprotective effect was indistinguishable membrane dopamine transporter (DAT), from the symptomatic improvement pro- which reflect the density of striatal dopa- vided by the drug on trial.1,2 To over- minergic nerve terminals,14-16 might be more come this limitation, a biological marker suitable for assessing disease progression of disease progression could be valuable and the efficacy of neuroprotective treat- to evaluate the efficacy of neuroprotec- ments. To test this, it is necessary to com- tive drugs. Until now, positron emission pare the striatal uptakes of PET DAT li- tomography (PET) using 18F-dopa has gands and 18F-dopa at different stages of PD. been the gold standard tool for measur- In addition, the relationships between each ing disease progression in patients with tracer’s uptake in the striatum and motor PD.3-5 However, 18F-dopa uptake reflects performance remain to be investigated in the the density of striatal dopaminergic ter- same cohort of patients with PD. We com- minals6 and the conversion of 18F-dopa into pared the striatal uptake of 18F-dopa with a Author affiliations are listed at 18F-dopamine in these terminals.5,7,8 It has highly specific DAT tropane ligand in pa- the end of this article. been suggested that in PD, the loss of do- tients with early and advanced PD and (REPRINTED) ARCH NEUROL / VOL 59, APR 2002 WWW.ARCHNEUROL.COM 580 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 PATIENTS AND METHODS magnetic resonance imaging. Of these 25 controls, 7 were examined with 18F-dopa only, 8 with 76Br-FE-CBT only, and 10 with both PET tracers. All patients and controls were PATIENTS part of ongoing protocols in our center (Orsay, France) that were approved by the local ethics committee, and they gave Eighteen patients (mean±SD age, 53.7±6.0 years) fulfill- their written informed consent after the nature of the pro- ing the UK Parkinson’s Disease Brain Bank criteria for pro- cedure had been fully explained. spective diagnosis of PD17 were selected. They were di- vided into 2 groups: (1) 10 patients with early PD (mean±SD MAGNETIC RESONANCE IMAGING age, 51.7±4.4 years; mean±SD disease duration, 1.9±0.6 AND PET ACQUISITION years; Hoehn and Yahr stage I-II) without atypical signs18 who were drug naive at the time of the PET study but re- Brain magnetic resonance images were obtained using a sponded to treatment after it was initiated and (2) 8 pa- 1.5-T imager (Signa; General Electric Co, Milwaukee, Wis). tients with more advanced PD (mean±SD age, 56.1±6.6 T2-weighted images from each patient were used to reveal years; mean±SD disease duration, 12.5±6.7 years; Hoehn brain lesions and signal abnormalities in the basal ganglia. and Yahr stage ՆIII) who were all dopa responders accord- In addition, a T1-weighted SPGR (spoiled gradient acqui- ing to the criteria of the Core Assessment Program for In- sition at the steady state) acquisition with inversion recov- tracerebral Transplantations and the Core Assessment Pro- ery was performed to allow 3-dimensional reconstruction gram for Surgical Interventional Therapies (Table 1).19,20 of magnetic resonance images. All patients were assessed in the “defined off” state19,20 Positron emission tomographic examinations in pa- using the Unified Parkinson’s Disease Rating Scale 3 tients with early PD were performed using the ECAT (UPDRS-3) motor score and the Purdue Pegboard task. The EXACT HR+ tomograph (CTI-Siemens, Knoxville, Tenn), latter estimates bradykinesia and has been shown to cor- which collects 63 simultaneous 2.4-mm-thick slices with relate with striatal dopaminergic function.21 Briefly, for this an intrinsic in-plane resolution of 4.3 mm.23 Patients with task, patients were asked to put as many unmarked rods advanced PD were studied using the ECAT 953B/31 to- as possible into aligned holes using a single hand in 30 sec- mograph (CTI-Siemens), which acquires 31 simultaneous onds. The number of rods accurately placed was regis- 3.4-mm-thick slices with an intrinsic transaxial resolu- tered. tion of 6.0 mm.24 For all PET examinations, patients were Patients were scanned using 2 different PET tracers: positioned in the tomograph using 3-dimensional laser (1) 18F-dopa and (2) 76Br-FE-CBT (fluorethyl-methyl-2␤- alignment and a thermoplastic mask molded to each pa- carboxymethoxy-3␤-4-bromophenyl-tropane), a ligand of tient’s face to restrain head movements. Tissue attenua- the presynaptic plasma membrane DAT.22 This highly spe- tion was measured using 3 68Ge rod sources. cific tracer has the advantage of reaching an equilibrium For 18F-dopa studies, patients with advanced disease 30 minutes after injection. Patients with PD were com- discontinued taking antiparkinsonian medications at least pared with 25 control subjects (22 men and 3 women; 12 hours before PET examination. In all patients, 100 mg mean±SD age, 49.7±13.0 years) with no neurological his- tory, no clinical abnormality, and normal findings on brain Continued on next page Table 1. Clinical Profile of 18 Patients With Parkinson Disease* Patient No./ Disease UPDRS-3 Score Sex/Age, y Duration, y (No Medication) Medication: mg/d 1/M/46 0.6 17.5 . 2/F/48 1.5 4.0 . 3/F/56 1.5 14.0 . 4/M/55 1.5 12.0 . 5/M/58 2.0 18.0 . 6/M/56 3.0 14.5 . 7/M/52 1.4 17.0 . 8/M/50 1.8 6.0 . 9/M/46 1.6 12.0 . 10/F/50 1.5 21.0 . 11/F/53 11.0 36.5 L-dopa: 650; pergolide mesylate: 5 12/M/59 7.0 66.0 L-dopa: 1200 13/F/60 16.0 51.0 L-dopa: 800; bromocriptine: 30; lisuride: 0.8 14/F/52 7.0 62.0 L-dopa: 800; selegiline hydrochloride: 10 15/F/49 11.0 59.0 L-dopa: 1200; bromocriptine: 60; apomorphine hydrochloride: 10 16/M/59 10.0 74.0 L-dopa: 1000; lisuride: 3; apomorphine hydrochloride: 3; selegiline hydrochloride: 10 17/M/46 8.0 65.0 L-dopa: 1250; lisuride: 1.2 18/F/66 27.0 36.5 L-dopa: 600; lisuride: 0.6; trihexyphenidyl hydrochloride: 4 *UPDRS-3 indicates Unified Parkinson’s Disease Rating Scale 3; ellipses, not applicable. (REPRINTED) ARCH NEUROL / VOL 59, APR 2002 WWW.ARCHNEUROL.COM 581 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 of carbidopa was given 1 hour before tracer administra- calculation of the striatal binding potential (BnP) values tion, and 9 time frames were acquired for 90 minutes after of this tracer using the graphical analysis described by intravenous injection of 143.9±55.1 MBq of 18F-dopa. For Logan et al27 and using the occipital activity as a nonspe- 76Br-FE-CBT studies, we tested the effect of dopaminergic cific input function.
Load more

Recommended publications
  • Biased Allosteric Regulation of the Prostaglandin F2α Receptor: From
    Biased Allosteric Regulation of the Prostaglandin F2 Receptor: From Small Molecules to Large Receptor Complexes By Eugénie Goupil Department of Pharmacology and Therapeutics McGill University, Montréal, Canada November, 2012 A thesis submitted to McGill in partial fulfillment of the requirements of the degree of Doctor of philosophy Copyright ©Eugénie Goupil, 2012 ''In theory, there is no difference between theory and practice. In practice, there is.'' -Lawrence Peter ''Yogi'' Berra ii Abstract G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors, and thus some of the most important targets for drug discovery. By binding to the orthosteric site where endogenous ligands bind, agonists and antagonists differentially modulate signals sent downstream from these receptors. New evidence suggests that GPCRs possess topographically distinct or allosteric binding sites, which may differentially modulate agonist- and antagonist-mediated responses to selectively affect distinct signalling pathways coupled to the same receptor. These sites may either positively or negatively regulate receptor activity, depending on the pathway in question, and thus can act as biased ligands, leading to functional selectivity (or ligand-directed signalling). Another way of allosterically regulating GPCR signalling is through receptor oligomerization, which has recently emerged as a common mechanism for regulating receptor function. The GPCR for prostaglandin F2 FP, is implicated in many important physiological responses, such as parturition, smooth muscle cell contraction and blood pressure regulation. Therefore, evaluating the potential use of allosteric modulators of FP to fine-tune PGF2-mediated signals, as well as generating a better understanding of its putative oligomerization partners would be of significant pharmacological and clinical interest.
    [Show full text]
  • Phencyclidine: an Update
    Phencyclidine: An Update U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse and Mental Health Administration Phencyclidine: An Update Editor: Doris H. Clouet, Ph.D. Division of Preclinical Research National Institute on Drug Abuse and New York State Division of Substance Abuse Services NIDA Research Monograph 64 1986 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administratlon National Institute on Drug Abuse 5600 Fishers Lane Rockville, Maryland 20657 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 NIDA Research Monographs are prepared by the research divisions of the National lnstitute on Drug Abuse and published by its Office of Science The primary objective of the series is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, and integrative research reviews. its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community. Editorial Advisors MARTIN W. ADLER, Ph.D. SIDNEY COHEN, M.D. Temple University School of Medicine Los Angeles, California Philadelphia, Pennsylvania SYDNEY ARCHER, Ph.D. MARY L. JACOBSON Rensselaer Polytechnic lnstitute National Federation of Parents for Troy, New York Drug Free Youth RICHARD E. BELLEVILLE, Ph.D. Omaha, Nebraska NB Associates, Health Sciences Rockville, Maryland REESE T. JONES, M.D. KARST J. BESTEMAN Langley Porter Neuropsychiatric lnstitute Alcohol and Drug Problems Association San Francisco, California of North America Washington, D.C. DENISE KANDEL, Ph.D GILBERT J. BOTV N, Ph.D. College of Physicians and Surgeons of Cornell University Medical College Columbia University New York, New York New York, New York JOSEPH V.
    [Show full text]
  • Lysergic Acid Diethylamide (LSD) Promotes Social Behavior Through Mtorc1 in the Excitatory Neurotransmission
    Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Danilo De Gregorioa,b,1, Jelena Popicb,2,3, Justine P. Ennsa,3, Antonio Inserraa,3, Agnieszka Skaleckab, Athanasios Markopoulosa, Luca Posaa, Martha Lopez-Canula, He Qianzia, Christopher K. Laffertyc, Jonathan P. Brittc, Stefano Comaia,d, Argel Aguilar-Vallese, Nahum Sonenbergb,1,4, and Gabriella Gobbia,f,1,4 aNeurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QC, Canada, H3A 1A1; bDepartment of Biochemistry, McGill University, Montreal, QC, Canada, H3A 1A3; cDepartment of Psychology, McGill University, Montreal, QC, Canada, H3A 1B1; dDivision of Neuroscience, Vita Salute San Raffaele University, 20132 Milan, Italy; eDepartment of Neuroscience, Carleton University, Ottawa, ON, Canada, K1S 5B6; and fMcGill University Health Center, Montreal, QC, Canada, H3A 1A1 Contributed by Nahum Sonenberg, November 10, 2020 (sent for review October 5, 2020; reviewed by Marc G. Caron and Mark Geyer) Clinical studies have reported that the psychedelic lysergic acid receptor (6), but also displays affinity for the 5-HT1A receptor diethylamide (LSD) enhances empathy and social behavior (SB) in (7–9). Several studies have demonstrated that LSD modulates humans, but its mechanism of action remains elusive. Using a glutamatergic neurotransmission and, indirectly, the α-amino- multidisciplinary approach including in vivo electrophysiology, 3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. optogenetics, behavioral paradigms, and molecular biology, the Indeed, in vitro studies have shown that LSD increased the ex- effects of LSD on SB and glutamatergic neurotransmission in the citatory response of interneurons in the piriform cortex following medial prefrontal cortex (mPFC) were studied in male mice.
    [Show full text]
  • Roles for the Uptake 2 Transporter OCT3 in Regulation Of
    Marquette University e-Publications@Marquette Biomedical Sciences Faculty Research and Publications Biomedical Sciences, Department of 2-2019 Roles for the Uptake2 Transporter OCT3 in Regulation of Dopaminergic Neurotransmission and Behavior Paul J. Gasser Marquette University, [email protected] Follow this and additional works at: https://epublications.marquette.edu/biomedsci_fac Part of the Neurosciences Commons Recommended Citation Gasser, Paul J., "Roles for the Uptake2 Transporter OCT3 in Regulation of Dopaminergic Neurotransmission and Behavior" (2019). Biomedical Sciences Faculty Research and Publications. 191. https://epublications.marquette.edu/biomedsci_fac/191 Marquette University e-Publications@Marquette Biomedical Sciences Faculty Research and Publications/College of Health Sciences This paper is NOT THE PUBLISHED VERSION; but the author’s final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation below. Neurochemistry International, Vol. 123, (February 2019): 46-49. DOI. This article is © Elsevier and permission has been granted for this version to appear in e-Publications@Marquette. Elsevier does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Elsevier. Roles for the Uptake2 Transporter OCT3 in Regulation of Dopaminergic Neurotransmission and Behavior Paul J. Gasser Department of Biomedical Sciences, Marquette University, Milwaukee, WI Abstract Transporter-mediated uptake determines the
    [Show full text]
  • Sex Differences in Serotonergic and Dopaminergic Mediation of LSD Discrimination in Rats
    Western Michigan University ScholarWorks at WMU Dissertations Graduate College 8-2017 Sex Differences in Serotonergic and Dopaminergic Mediation of LSD Discrimination in Rats Keli A. Herr Western Michigan University, [email protected] Follow this and additional works at: https://scholarworks.wmich.edu/dissertations Part of the Psychology Commons Recommended Citation Herr, Keli A., "Sex Differences in Serotonergic and Dopaminergic Mediation of LSD Discrimination in Rats" (2017). Dissertations. 3170. https://scholarworks.wmich.edu/dissertations/3170 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. SEX DIFFERENCES IN SEROTONERGIC AND DOPAMINERGIC MEDIATION OF LSD DISCRIMINATION IN RATS by Keli A Herr A dissertation submitted to the Graduate College in partial fulfillment of the requirements for the degree of Doctor of Philosophy Psychology Western Michigan University August 2017 Doctoral Committee: Lisa Baker, Ph.D., Chair Cynthia Pietras, Ph.D. Heather McGee, Ph.D. Missy Peet, Ph.D. SEX DIFFERENCES IN SEROTONERGIC AND DOPAMINERGIC MEDIATION OF LSD DISCRIMINATION IN RATS Keli A. Herr, Ph.D. Western Michigan University After decades of opposition, a resurgence of interest in the psychotherapeutic potential of LSD is gaining acceptance in the medical community. Future acceptance of LSD as a psychotherapeutic adjuvant may be predicated on knowledge about its neural mechanisms of action. Preclinical drug discrimination assay offers an invaluable model to determine the neural mechanisms underlying LSD’s interoceptive stimulus effects.
    [Show full text]
  • Dopamine Agonists 1
    VA/DoD Drug Class Review: Dopamine Agonists 1 VA/DoD Drug Class Review: Dopamine Agonists Department of Defense Pharmacoeconomic Center (DoD PEC) Department of Veterans Affairs Pharmacy Benefits Management Strategic Healthcare Group (VA PBM) and the VA Medical Advisory Panel (VA MAP) Introduction The purpose of this review is to evaluate whether the dopamine agonists (DA) are therapeutically interchangeable. The dopamine agonists are subcategorized as ergoline and non-ergoline. The ergoline compounds (bromocriptine and pergolide) are derived from the ergot alkaloids. The non-ergoline compounds include pramipexole and ropinirole. Though the exact mechanism of action in Parkinsonism is unknown, all of the dopamine agonists are thought to work by directly stimulating postsynaptic dopaminergic receptors in the nigrostriatal system. The two ergoline agents were introduced into the market in the 1980’s. Only bromocriptine, which was FDA- approved prior to January 1, 1982, is available in generic form. Table 1: Dopamine agonists available in the U.S for the treatment of Parkinson’s disease Strengths & FDA approval Generic Brand (Manufacturer) formulations date Bromocriptine Parlodel (Novartis); Generics Tablets 2.5, and 5 mg N/A* available Pergolide Permax (Amarin) Generics Tablets 0.05, 0.25, and 1 mg 12/30/88 availab le** Pramipexole Mirapex (Pharmacia) Tablets 0.125, 0.25, 0.5, 1, 7/1/97 and 1.5 mg Ropinirole Requip (SKB) Tablets 0.25, 0.5, 1, 2, 3, 4 9/19/97 and 5 mg *Parlodel was approved prior to Jan 1, 1982. ** pergolide was voluntarily withdrawn from the market on March 29, 2007 Parkinson’s Disease is a degenerative brain disorder that affects approximately 500,000 to 1 million people in the United States.
    [Show full text]
  • Phencyclidine Increases Forebrain Monoamine Metabolism in Rats and Monkeys: Modulation by the Isomers of HA966
    The Journal of Neuroscience, March 1, 1997, 17(5):1769–1775 Phencyclidine Increases Forebrain Monoamine Metabolism in Rats and Monkeys: Modulation by the Isomers of HA966 J. David Jentsch,1 John D. Elsworth,2,3 D. Eugene Redmond Jr.,2,4 and Robert H. Roth2,3 Departments of 1Neurobiology, 2Psychiatry, 3Pharmacology, and 4Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06510 The noncompetitive NMDA receptor antagonist phencyclidine enantiomer altered the effect of PCP on DA turnover in the (PCP) has psychotomimetic properties in humans and activates nucleus accumbens or the PCP-induced increases in serotonin the frontal cortical dopamine innervation in rats, findings that turnover in PFC. PCP (0.3 mg/kg, i.m.) exerted regionally se- have contributed to a hyperdopaminergic hypothesis of schizo- lective effects on the dopaminergic and serotonergic innerva- phrenia. In the present studies, the effects of the enantiomers of tion of the monkey frontal cortex, effects blocked by pretreat- 3-amino-1-hydroxypyrrolid-2-one (HA966) on PCP-induced ment with S-(2)HA966 (3 mg/kg, i.m.). Importantly, these data changes in monoamine metabolism in the forebrain of rats and demonstrate that in the primate, PCP has potent effects on monkeys were examined, because HA966 has been shown dopamine transmission in the frontal cortex, a brain region previously to attenuate stress- or drug-induced activation of thought to be dysfunctional in schizophrenia. In addition, a role dopamine systems. In rats, PCP (10 mg/kg, i.p.) potently acti- for S-(2)HA966 as a modulator of cortical monoamine trans- vated dopamine (DA) turnover in the medial prefrontal cortex mission in primates is posited.
    [Show full text]
  • Molecular Regulation in Dopaminergic Neuron Development
    International Journal of Molecular Sciences Review Molecular Regulation in Dopaminergic Neuron Development. Cues to Unveil Molecular Pathogenesis and Pharmacological Targets of Neurodegeneration Floriana Volpicelli 1 , Carla Perrone-Capano 1,2 , Gian Carlo Bellenchi 2,3, Luca Colucci-D’Amato 4,* and Umberto di Porzio 2 1 Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; fl[email protected] (F.V.); [email protected] (C.P.C.) 2 Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, 80131 Rome, Italy; [email protected] (G.C.B.); [email protected] (U.d.P.) 3 Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy 4 Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy * Correspondence: [email protected]; Tel.: +39-0823-274577 Received: 28 April 2020; Accepted: 1 June 2020; Published: 3 June 2020 Abstract: The relatively few dopaminergic neurons in the mammalian brain are mostly located in the midbrain and regulate many important neural functions, including motor integration, cognition, emotive behaviors and reward. Therefore, alteration of their function or degeneration leads to severe neurological and neuropsychiatric diseases. Unraveling the mechanisms of midbrain dopaminergic (mDA) phenotype induction and maturation and elucidating the role of the gene network involved in the development and maintenance of these neurons is of pivotal importance to rescue or substitute these cells in order to restore dopaminergic functions. Recently, in addition to morphogens and transcription factors, microRNAs have been identified as critical players to confer mDA identity. The elucidation of the gene network involved in mDA neuron development and function will be crucial to identify early changes of mDA neurons that occur in pre-symptomatic pathological conditions, such as Parkinson’s disease.
    [Show full text]
  • Development and Differentiation of Midbrain Dopaminergic
    cells Review Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside Mengmeng Wang 1,2,3, King-Hwa Ling 4,5 , Jun Jie Tan 3,* and Cheng-Biao Lu 1,2,* 1 Department of Neurobiology and Physiology, Xinxiang Medical University, Xinxiang 453003, Henan, China; [email protected] 2 The International-Joint Lab for Non-invasive Neural Modulation/Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University, Xinxiang 453003, Henan, China 3 Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200, Kepala Batas, Penang, Malaysia 4 Department of Biomedical Sciences, Faculty of Medicine, Universiti Putra Malaysia, Seri Kembangan 43400 Selangor, Malaysia; [email protected] 5 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA * Correspondence: [email protected] (J.J.T.); [email protected] (C.-B.L.); Tel.: +604-56-22-422 (J.J.T.); +86-15537391797 (C.-B.L.) Received: 10 April 2020; Accepted: 12 June 2020; Published: 18 June 2020 Abstract: Parkinson’s Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients.
    [Show full text]
  • Emulated Clinical Trials from Longitudinal Real-World
    Supplemental Material for “Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson's Disease” Table S1. ICD codes for PD cohort definition Type System Code Name icd9 3320 Paralysis agitans Inclusion icd10 G20 Parkinson's disease icd9 3316 Corticobasal degeneration icd9 3321 Secondary parkinsonism icd9 3330 Other degenerative diseases of the basal ganglia Exclusion icd10 G21 Secondary parkinsonism Progressive supranuclear ophthalmoplegia [Steele- icd10 G231 Richardson-Olszewski] icd10 G3185 Corticobasal degeneration Table S2. PD-indicated drugs and their corresponding ATC class names. The list below has been compiled by a domain expert based on the following sources: National Drug File – Reference Terminology (NDF-RT), Anatomical Therapeutic Chemical Classification System (ATC), and DrugBank (45). Drug ATC class code(s) ATC class name(s) Amantadine N04BB Adamantane derivatives Drugs used in erectile dysfunction; dopamine Apomorphine G04BE; N04BC agonists Belladonna alkaloids, tertiary amines; Atropine A03BA; S01FA anticholinergics Benztropine N04AC Ethers of tropine or tropine derivatives Biperiden N04AA Tertiary amines Bornaprine N04AA Tertiary amines Bromocriptine G02CB; N04BC Prolactine inhibitors; dopamine agonists Budipine N04BX Other dopaminergic agents Cabergoline G02CB; N04BC Prolactine inhibitors; dopamine agonists Carbidopa N/A N/A Dexetimide N04AA Tertiary amines Dihydroergocryptine N04BC Dopamine agonists Entacapone N04BX Other
    [Show full text]
  • The Kappa Opioid Agonist, Salvinorin A, Attenuates Locomotor Effects of Morphine but Not Morphine-Induced Conditioned Place Preference
    Western Michigan University ScholarWorks at WMU Master's Theses Graduate College 6-2012 The Kappa Opioid Agonist, Salvinorin A, Attenuates Locomotor Effects of Morphine but not Morphine-Induced Conditioned Place Preference Stacy Dianne Engebretson Follow this and additional works at: https://scholarworks.wmich.edu/masters_theses Part of the Psychology Commons Recommended Citation Engebretson, Stacy Dianne, "The Kappa Opioid Agonist, Salvinorin A, Attenuates Locomotor Effects of Morphine but not Morphine-Induced Conditioned Place Preference" (2012). Master's Theses. 67. https://scholarworks.wmich.edu/masters_theses/67 This Masters Thesis-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Master's Theses by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. THE KAPPA OPIOID AGONIST, SALVINORIN A, ATTENUATES LOCOMOTOR EFFECTS OF MORPHINE BUT NOT MORPHINE-INDUCED CONDITIONED PLACE PREFERENCE by Stacy Dianne Engebretson A Thesis Submitted to the Faculty of the Graduate College in partial fulfillment of the requirements for the Degree of Master of Arts Department of Psychology Advisor: Lisa E. Baker, Ph. D. Western Michigan University Kalamazoo, Michigan June 2012 THE GRADUATE COLLEGE WESTERN MICHIGAN UNIVERSITY KALAMAZOO, MICHIGAN Date May 23, 2012 WE HEREBY APPROVE THE THESIS SUBMITTED BY Stacy Dianne Engebretson ENTITLED The Kappa Opioid Agonist, Salvinorin A, Attenuates Locomotor Effects of Morphine but Not Morphine-Induced Conditioned Place Preference. AS PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Master of Arts Psychology (Department) Thesis Committee Behavior Analysis ®4o^Q& (Program) Alan D. Poling, Ph.! Thesis Committee Memf APPROVED s$AM>sr\ Date UlUL U\l Dean of>f The Graduate College THE KAPPA OPIOID AGONIST, SALVINORIN A, ATTENUATES LOCOMOTOR EFFECTS OF MORPHINE BUT NOT MORPHINE-INDUCED CONDITIONED PLACE PREFERENCE Stacy Dianne Engebretson, M.A.
    [Show full text]
  • Involvement of Dopamine D2 and 5-HT IA Receptors in Roxindole-Induced Antinociception
    Indi an Journal of Experiment al Biology Vol. 37, March 1999, pp. 23 4-237 Involvement of dopamine D2 and 5-HT IA receptors in roxindole-induced antinociception Ipe Ninan & S K Kulkarni* Ph armaco logy Di vision, Universit y In stitute of Pharmaceutical Sciences, Panj ab Uni versity, Chand igarh )60014, Indi a Received 23 March 1998; revi sed 27 November 1998 Rox i Il dole. a DA O2 receptor ago ni st (2-1 6 mglkg) produ ced dose-dependent i ncrease in percent age <I ntinociceptio nT he effect whi ch was bl ocked by DA O2 antago ni st (-)s ulpiride (50 mglkg) and 5-HTIAr eceptor antagoni st (-) pin do lol (5 mg/kgl. Rox in do le (4 and 8 mglkg) reversed both nalo xo ne (20 mglkg)-induced hyperalgesia and reserpine (2 mg/kg)-i nduced hyperalgesia. Th is reversal was sensiti ve to blockade by both (-)su lpiri cte (50 mglkg) and (-) pindolol (5 mg/kg). The presen t stud y s~ges t s th at ro xindol e-induced ant inocicepti on is mediated by postsynaptic DA D2 and 5-HTIA rece pt ors. Rox indole (EMD 49980) is a representati ve of a new severe pain associated with various states of di sease class of dopaminergic drugs, I. e., the indolyl affecting the nervous system, such as. the thalamic butylamines. whi ch lac k structural similarities with syndrome, herpes zoster and Parkinson's either ri gid dopamine (DA ) analogs or ergot di sease' 1.l 2.'J.'4. and a recent study showed that 8-0H deri vatives '.
    [Show full text]