DOCSLIB.ORG

A Novel Method for Creating a Synthetic L-DOPA Proteome and in Vitro Evidence of Incorporation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Novel Method for Creating a Synthetic L-DOPA Proteome and in Vitro Evidence of Incorporation proteomes Article A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation Joel Ricky Steele 1,2,* , Natalie Strange 3 , Kenneth J. Rodgers 2 and Matthew P. Padula 1 1 Proteomics Core Facility and School of Life Sciences, The University of Technology Sydney, Ultimo, NSW 2007, Australia; [email protected] 2 Neurotoxin Research Group, School of Life Sciences, The University of Technology Sydney, Ultimo, NSW 2007, Australia; [email protected] 3 School of Life Sciences, The University of Technology Sydney, Ultimo, NSW 2007, Australia; [email protected] * Correspondence: [email protected] Abstract: Proteinopathies are protein misfolding diseases that have an underlying factor that affects the conformation of proteoforms. A factor hypothesised to play a role in these diseases is the incorporation of non-protein amino acids into proteins, with a key example being the therapeutic drug levodopa. The presence of levodopa as a protein constituent has been explored in several studies, but it has not been examined in a global proteomic manner. This paper provides a proof-of-concept method for enzymatically creating levodopa-containing proteins using the enzyme tyrosinase and provides spectral evidence of in vitro incorporation in addition to the induction of the unfolded protein response due to levodopa. Keywords: misincorporation; post-translational modifications; PTM; Levodopa; L-DOPA Citation: Steele, J.R.; Strange, N.; Rodgers, K.J.; Padula, M.P. A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro 1. Introduction Evidence of Incorporation. Proteomes 2021, 9, 24. https://doi.org/10.3390/ The non-protein amino acid (NPAA) L-3,4-dihydroxyphenylalanine (L-DOPA), com- proteomes9020024 mercially known as ‘levodopa’, is used to restore dopamine levels in the damaged substan- tia nigra of Parkinson’s disease (PD) patients [1] although it has also been hypothesised to Academic Editors: Jacek accelerate PD pathology and neurodegeneration [2] by causing neuronal toxicity [2–16]. R. Wisniewski and Gunnar Dittmar The mechanisms of L-DOPA-induced neurodegeneration include induction of oxidative stress and the misincorporation of L-DOPA into proteins in place of L-tyrosine, resulting in Received: 19 March 2021 protein misfolding and the formation of proteolysis-resistant aggregates [3,5,7,17–19]. To Accepted: 18 May 2021 date, in vitro studies have not examined or identified the proteins containing incorporated Published: 24 May 2021 L-DOPA and their potential role in disease pathology, with Parkinson’s disease datasets being a prime candidate [20]. Publisher’s Note: MDPI stays neutral Protein-bound DOPA (PB-DOPA) can form via several mechanisms, including direct with regard to jurisdictional claims in incorporation of free L-DOPA in place of tyrosine into a growing polypeptide chain [21]. published maps and institutional affil- Alternatively, L-DOPA can be formed via hydroxyl attack on tyrosine residues by a reactive iations. oxygen species (ROS) [21–25], independent of free L-DOPA. Similarly, hydroxyl radical attack on the phenyl ring of phenylalanine residues forms isomers of tyrosine [22,26], the position of the hydroxyl group of these isomers (meta and ortho) differing from that of the protein amino acid L-tyrosine (para-tyrosine) (Figure1). It is known that free L-DOPA can Copyright: © 2021 by the authors. induce oxidative stress, resulting in ROS generation via interaction with iron and copper Licensee MDPI, Basel, Switzerland. to produce Fenton reaction products [27], which leads to further hydroxylation of free or This article is an open access article protein incorporated tyrosine, thereby producing free and PB-DOPA [5,22]. distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Proteomes 2021, 9, 24. https://doi.org/10.3390/proteomes9020024 https://www.mdpi.com/journal/proteomes Proteomes 2021, 9, x Proteomes 2021, 9, 24 2 of 16 2 of 15 Figure 1. Structural forms of phenylalanine, para-tyrosine, meta-tyrosine, ortho-tyrosine, and L-DOPA. Hydroxyl radical attackFigure on the phenyl 1. Structural ring of phenylalanine forms of phenylalanine, residues can form isomerspara-tyrosine, of tyrosine, meta-tyrosin the canonical forme, ortho-tyrosine, being para-tyrosine, but canand also L-DOPA. form meta-tyrosine Hydroxyl and ortho-tyrosine;radical attack hydroxyl on the attack phenyl of tyrosine ring of can phenylalanine also form L-DOPA. residues can form isomers of tyrosine, the canonical form being para-tyrosine, but can also form The misincorporation rate of canonical amino acids in general is reported to be approx- meta-tyrosine andimately ortho-tyrosine; one in 10,000; hydroxyl this low attack level of of misincorporation tyrosine can also makes form it difficult L-DOPA. to detect DOPA incorporation or other misincorporated amino acids [18,21,28,29]. However, it is possible The misincorporation rate of canonical amino acids in general is reported to be ap- that misincorporation levels of NPAAs could be higher since they can escape proofreading proximately one inmechanisms 10,000; this that low have level evolved of misincorporation to detect the mistaken makes incorporation it difficult of a to canonical detect amino DOPA incorporationacid. or As other proteomics misincorporated utilises mass spectrometers, amino acids which [18,21,28,29]. are concentration-dependent However, it is detec- possible that misincorporationtors, methodologies levels should of beNP appliedAAs could to enhance be higher the ability since to detect they these can low-abundanceescape proofreading mechanismsspecies (for that a comprehensive have evolved review, to detect see Steele the mistaken et al., 2021 [incorporation28]). The most sensitive of a ca- way to nonical amino acid.detect As low-abundanceproteomics utilises species mass in exploratory spectrometers, proteomics which is the are use concentration- of data-independent acquisition (DIA), but this requires prior identification of the peptide species and its frag- dependent detectors, methodologies should be applied to enhance the ability to detect ments for a searchable spectral library, especially in instances of modified peptides [29]. By these low-abundanceproducing species synthetic (for a comprehensive peptides for subsequent review, proteomic see Steele analysis et al., and2021 library [28]). inclusion,The it most sensitive waybecomes to detect possible low-abundance to identify very species low levels in exploratory of the modified proteomics proteoform. is the However, use the of data-independentproduction acquisition of such (DIA), a synthetic but this library requires is prohibitively prior identification expensive and of the the libraries peptide currently species and its fragmentsavailable for do nota searchable contain NPAA spectral modifications library, [ 30especially]. in instances of mod- ified peptides [29]. ByThe produc best measureing synthetic of the global peptides oxidative for state subsequent of a proteome proteomic is the level analysis of methionine oxidation, which occurs via the addition of a single oxygen atom, creating methionine and library inclusion,sulfoxide it becomes with a masspossible shift to of identify +15.99 Da, very homologous low levels to of that the of modified hydroxylation pro- [31,32]. teoform. However,However, the production protein extraction of such anda synthetic preparation library can increase is prohibitively the likelihood expensive of forming oxi- and the libraries currentlydised methionine available and do even not electrospray contain NPAA ionisation mo candifications result in this [30]. modification [29,33,34]. The best measureDue to of the the multiple global possibleoxidative end-points state of a of proteome hydroxyl attack, is the thelevel identification of methionine of oxidised oxidation, which phenylalanineoccurs via the may addition help in determining of a single if oxygen PB-DOPA atom, has been creating formed methionine from incorporation sulfoxide with a massor from shift hydroxyl of +15.99 attack. Da, Within homo plantlogous and animalto that tissues, of hydroxylation the conversion [31,32]. of tyrosine to L-DOPA can be carried out by the enzyme tyrosinase, which has also been used in indus- However, proteintrial extraction synthesis and of L-DOPA preparation and is can essential increase to the the production likelihood of dopamineof forming in theoxi- human dised methioninebrain and [33 even,34]. Unlike electrospray oxidation reactions,ionisation the enzymecan result tyrosinase in this has themodification capacity to generate [29,33,34]. Due to peptide-bondedthe multiple possible DOPA (from end-poin PB-tyrosinets of hydroxyl conversion) attack, without the generating identification other of oxidised oxidised phenylalanineamino acidmay residues help in such determining as ortho- and if meta-tyrosine.PB-DOPA has been formed from in- corporation or from hydroxylTo overcome attack. the poor Within detection plant of and low-ion-abundance animal tissues, peptides the conversion from PB-DOPA of pro- teoforms, a method for creating a positive control spectral library needs to be produced tyrosine to L-DOPA can be carried out by the enzyme tyrosinase, which has also been to enable future application to clinical samples by enabling DIA analyses. A method for used in industrialgenerating synthesis aof positive L-DOPA control and spectralis essential library to andthe
Load more

Recommended publications
  • Substantia Nigra Integrity Correlates with Sequential Working Memory in Parkinson’S Disease
    Research Articles: Behavioral/Cognitive Substantia nigra integrity correlates with sequential working memory in Parkinson’s disease https://doi.org/10.1523/JNEUROSCI.0242-21.2021 Cite as: J. Neurosci 2021; 10.1523/JNEUROSCI.0242-21.2021 Received: 1 February 2021 Revised: 6 May 2021 Accepted: 12 May 2021 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.jneurosci.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2021 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. 1 Research Article 2 Substantia nigra integrity correlates with sequential working 3 memory in Parkinson’s disease 4 Running title: substantia nigra & sequential memory in PD 5 Wenyue Liu 1,2, Changpeng Wang 3, Tingting He 3, Minghong Su 2,4, Yuan Lu 1, 6 Guanyu Zhang 2,4, Thomas F. Münte 5, Lirong Jin 3,*, Zheng Ye 1,6,* 7 1Institute of Neuroscience, Key Laboratory of Primate Neurobiology, Center for 8 Excellence in Brain Science and Intelligence Technology, Chinese Academy of 9 Sciences, Shanghai 200031, China 10 2University of Chinese Academy of Sciences, Beijing 100049, China 11 3Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032, 12 China 13 4Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China 14 5Department of Neurology, University of Lübeck, Lübeck 23538, Germany 15 6Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, 16 Shanghai 201210, China 17 18 WL, CW, and TH equally contributed to this work.
    [Show full text]
  • Contrast Mechanisms Associated with Neuromelanin-MRI
    Contrast mechanisms associated with Neuromelanin-MRI Paula Trujillo1,2, Paul Summers1, Emanuele Ferrari3, Fabio A. Zucca3, Michela Sturini4, Luca Mainardi2, Sergio Cerutti2, Alex K Smith5,6, Seth A Smith5,6,7, Luigi Zecca3, Antonella Costa1 1 Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI, Italy 2 Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, MI, Italy 3 Institute of Biomedical Technologies, National Research Council of Italy, Segrate, MI, Italy 4 Department of Chemistry, University of Pavia, Pavia, PV, Italy 5 Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA 6 Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA 7 Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA Full postal and email address of the corresponding author: Paula Trujillo Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Department of Neuroradiology Via F. Sforza 35 20122, Milan, MI, Italy Email: [email protected] Abbreviations: BSA = bovine serum albumin; DS = direct saturation; LC = locus coeruleus; MT = magnetization transfer; NM = Neuromelanin; PD = Parkinson’s Disease; PSR = pool size ratio; qMT = quantitative MT; RF = radiofrequency; SN = Substantia Nigra; TSE = turbo spin echo. Abstract Purpose: To investigate the physical mechanisms associated with the contrast observed in neuromelanin-MRI. Methods: Phantoms having different concentrations of synthetic melanins with different degrees of iron loading were examined on a 3T scanner using relaxometry and quantitative magnetization transfer (MT). Results: Concentration-dependent T1- and T2-shortening was most pronounced for the melanin pigment when combined with iron. Metal-free melanin had a negligible effect on the magnetization transfer spectra.
    [Show full text]
  • Testosterone for Women...And Men
    Testosterone for Women...and Men Date: 05/08/2006 Posted By: Jon Barron Every now and then I get a break in putting together a newsletter. I get to steal the entire newsletter from myself. In this case, I was able to take most of the material for this newsletter from the formulation information I put together for my new upgraded Women's Formula that Baseline Nutritionals released this month. And while this newsletter definitely serves as an introduction to that new formula, it more importantly provides an excuse for exploring a crucial topic for both men and women -- the value of maintaining an optimum testosterone balance. However, before we get into the specifics of both the men's and women's formulas, let's explore what testosterone does in the body -- and why it's so important for both men and women. The 30,000 Mile Tune-Up: Hormonal Changes As men and women enter their 30's, profound changes begin to take place in their bodies. If not addressed (that's the 30,000 mile tune-up thing), these changes can lead to, among other things: • Decreased energy and zest for life • Loss of muscle tone and increased fat • Circulatory problems and decreased libido But it doesn't have to be this way. Let me explain. Hormonal Imbalance Hormones are the body's chemical messenger system. They tell the various cells of the body what to do - - and when to do it -- by attaching to specific receptor sites on individual cells. Problems occur when the various hormones get out of balance.
    [Show full text]
  • Failure of Vitamin B6 to Reverse the L-Dopa Effect in Patients on a Dopa Decarboxylase Inhibitor
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.682 on 1 December 1971. Downloaded from J. Neurol. Neurosurg. Psychiat., 34, 682-686 Failure of vitamin B6 to reverse the L-dopa effect in patients on a dopa decarboxylase inhibitor HAROLD L. KLAWANS, STEVEN P. RINGEL. AND DAVID M. SHENKER From the Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA SUMMARY Seven patients with Parkinsonism previously on L-dopa were placed on a regimen of L-dopa and alpha methyl dopa hydrazine (a dopa decarboxylase inhibitor). Two of these patients had previously shown marked clinical deterioration of the L-dopa improvement when given pyrid- oxine. None of the seven patients receiving alpha methyl dopa hydrazine demonstrated any change in their condition when given pyridoxine. The failure of vitamin B6 to reverse the clinical effect of L-dopa in patients receiving both L-dopa and a peripheral dopa decarboxylase inhibitor suggests that reversal of the L-dopa effect induced by vitamin B6 is due to increasing the activity of the enzyme dopa decarboxylase outside the central nervous system. guest. Protected by copyright. In patients with Parkinsonism receiving L-dopa hydrazine). These observations help to explain the (L-3, 4-dihydroxyphenylalanine), vitamin B6 has paradoxical effects of large amounts of pyridoxine recently been shown to cause a loss or reversal of in patients receiving L-dopa. the L-dopa effect (Duvoisin, Yahr, and Cote, 1969; Yahr, Duvoisin, Schear, Barrett, and Hoehn, METHODS AND RESULTS 1970). This was discovered when Duvoisin et al. (1969) gave vitamin B6 to patients receiving L-dopa Seven patients with Parkinsonism who had been on in an attempt to increase formation of dopamine L-dopa for at least one year were included in this from L-dopa within the central nervous system (CNS) study.
    [Show full text]
  • Neuromelanin MR Imaging in Parkinson's Disease
    Oruen – The CNS Journal Review article Neuromelanin MR imaging in Parkinson’s disease Sofia Reimão1,2,4, Joaquim J Ferreira3,4,5,6 1 Neurological Imaging Department, Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Portugal 2 Imaging University Clinic, Faculty of Medicine, University of Lisbon, Portugal 3 Department of Neurosciences, Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Portugal 4 Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal 5 Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal 6 CNS – Campus Neurológico Sénior, Torres Vedras, Portugal Received – 24 April 2016; accepted – 04 May 2016 ABSTRACT The development and application of neuromelanin sensitive MR imaging has allowed the detection of significant changes in the substantia nigra (SN) of Parkinson’s disease (PD) patients, with high sensitivity and specificity in differentiating PD patients from non-PD aged controls, even in early disease stages, namely at the time of clinical diagnosis. These MR neuromelanin changes in the SN of PD patients reproduced in vivo long known characteristic pathological changes of PD. Several image evaluation methods have been used, corroborating the reproducibility of the data and enabling wider applications of this imaging technique in the clinical practice. In this review we analyze the background and the technical aspects of neuromelanin sensitive MR imaging, focusing on the applications of these specific
    [Show full text]
  • The Pharmacological Properties and Therapeutic Use of Apomorphine
    Molecules 2012, 17, 5289-5309; doi:10.3390/molecules17055289 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review The Pharmacological Properties and Therapeutic Use of Apomorphine Samo Ribarič 1,2 1 Institute of Pathophysiology, Medical Faculty, University of Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia; E-Mail: [email protected]; Tel.: +386-1-543-70-20; Fax: +386-1-543-70-21 2 Laboratory for Movement Disorders, Department of Neurological Disorders, University Clinical Centre Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia Received: 1 March 2012; in revised form: 22 April 2012 / Accepted: 25 April 2012 / Published: 7 May 2012 Abstract: Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D1, D2S, D2L, D3, D4, and D5 receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT1A, 5HT2A, 5HT2B, and 5HT2C), and α-adrenergic receptors (α1B, α1D, α2A, α2B, and α2C). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (i.e., to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation.
    [Show full text]
  • Semi-Automatic Signature-Based Segmentation Method for Quantification of Neuromelanin in Substantia Nigra
    brain sciences Article Semi-Automatic Signature-Based Segmentation Method for Quantification of Neuromelanin in Substantia Nigra Gašper Zupan 1, Dušan Šuput 1,* , Zvezdan Pirtošek 1,2 and Andrej Vovk 1 1 Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; [email protected] (G.Z.); [email protected] (Z.P.); [email protected] (A.V.) 2 Department of Neurology, University Medical Center, Zaloška 2, 1000 Ljubljana, Slovenia * Correspondence: [email protected]; Tel.: +386-1-543-7821 Received: 23 October 2019; Accepted: 19 November 2019; Published: 22 November 2019 Abstract: In Parkinson’s disease (PD), there is a reduction of neuromelanin (NM) in the substantia nigra (SN). Manual quantification of the NM volume in the SN is unpractical and time-consuming; therefore, we aimed to quantify NM in the SN with a novel semi-automatic segmentation method. Twenty patients with PD and twelve healthy subjects (HC) were included in this study. T1-weighted spectral pre-saturation with inversion recovery (SPIR) images were acquired on a 3T scanner. Manual and semi-automatic atlas-free local statistics signature-based segmentations measured the surface and volume of SN, respectively. Midbrain volume (MV) was calculated to normalize the data. Receiver operating characteristic (ROC) analysis was performed to determine the sensitivity and specificity of both methods. PD patients had significantly lower SN mean surface (37.7 8.0 vs. ± 56.9 6.6 mm2) and volume (235.1 45.4 vs. 382.9 100.5 mm3) than HC. After normalization ± ± ± with MV, the difference remained significant.
    [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]
  • Medications to Be Avoided Or Used with Caution in Parkinson's Disease
    Medications To Be Avoided Or Used With Caution in Parkinson’s Disease This medication list is not intended to be complete and additional brand names may be found for each medication. Every patient is different and you may need to take one of these medications despite caution against it. Please discuss your particular situation with your physician and do not stop any medication that you are currently taking without first seeking advice from your physician. Most medications should be tapered off and not stopped suddenly. Although you may not be taking these medications at home, one of these medications may be introduced while hospitalized. If a hospitalization is planned, please have your neurologist contact your treating physician in the hospital to advise which medications should be avoided. Medications to be avoided or used with caution in combination with Selegiline HCL (Eldepryl®, Deprenyl®, Zelapar®), Rasagiline (Azilect®) and Safinamide (Xadago®) Medication Type Medication Name Brand Name Narcotics/Analgesics Meperidine Demerol® Tramadol Ultram® Methadone Dolophine® Propoxyphene Darvon® Antidepressants St. John’s Wort Several Brands Muscle Relaxants Cyclobenzaprine Flexeril® Cough Suppressants Dextromethorphan Robitussin® products, other brands — found as an ingredient in various cough and cold medications Decongestants/Stimulants Pseudoephedrine Sudafed® products, other Phenylephrine brands — found as an ingredient Ephedrine in various cold and allergy medications Other medications Linezolid (antibiotic) Zyvox® that inhibit Monoamine oxidase Phenelzine Nardil® Tranylcypromine Parnate® Isocarboxazid Marplan® Note: Additional medications are cautioned against in people taking Monoamine oxidase inhibitors (MAOI), including other opioids (beyond what is mentioned in the chart above), most classes of antidepressants and other stimulants (beyond what is mentioned in the chart above).
    [Show full text]
  • A Mechanistic Account of Striatal Dopamine Function in Human Cognition: Psychopharmacological Studies with Cabergoline and Haloperidol
    Behavioral Neuroscience Copyright 2006 by the American Psychological Association 2006, Vol. 120, No. 3, 497–517 0735-7044/06/$12.00 DOI: 10.1037/0735-7044.120.3.497 A Mechanistic Account of Striatal Dopamine Function in Human Cognition: Psychopharmacological Studies With Cabergoline and Haloperidol Michael J. Frank Randall C. O’Reilly University of Arizona University of Colorado at Boulder The authors test a neurocomputational model of dopamine function in cognition by administering to healthy participants low doses of D2 agents cabergoline and haloperidol. The model suggests that DA dynamically modulates the balance of Go and No-Go basal ganglia pathways during cognitive learning and performance. Cabergoline impaired, while haloperidol enhanced, Go learning from positive rein- forcement, consistent with presynaptic drug effects. Cabergoline also caused an overall bias toward Go responding, consistent with postsynaptic action. These same effects extended to working memory and attentional domains, supporting the idea that the basal ganglia/dopamine system modulates the updating of prefrontal representations. Drug effects interacted with baseline working memory span in all tasks. Taken together, the results support a unified account of the role of dopamine in modulating cognitive processes that depend on the basal ganglia. Keywords: basal ganglia, dopamine, cognition, computational, psychopharmacology The basal ganglia (BG) participate in various aspects of cogni- Carter, Noll, & Cohen, 2003; Willcutt et al., 2005). Consequently, tion and
    [Show full text]
  • Insights Into Parkinson's Disease from Computational Models Of
    bioRxiv preprint doi: https://doi.org/10.1101/260992; this version posted February 12, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Insights into Parkinson's disease from computational models of the basal ganglia Mark D. Humphries1;2∗, Jose Obeso3 and Jakob Kisbye Dreyer4;5 1. Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK. 2. Department of Psychology, University of Nottingham, Nottingham, UK 3. HM-CINAC,Hospital Puerta del Sur, Mostoles, CEU-San Pablo University and CIBERNED, Instituto Carlos III, Madrid, Spain 4. Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark 5. Department of Bioinformatics, H Lundbeck A/S, DK-2500 Valby, Denmark ∗ Corresponding author: [email protected] Abstract Movement disorders arise from the complex interplay between multiple changes to neural circuits, and between those changes and their compensatory mechanisms. Treatments, when available, either have incompletely understood mechanisms of ac- tion, or unknown routes from these mechanisms to the amelioration of the disorder's symptoms. Using Parkinson's disease as a case-study, we review here how compu- tational models are a crucial tool for taming this complexity, across causative mech- anisms, consequent neural dynamics, and treatments. For mechanisms, we review models that capture the effects of losing dopamine on basal ganglia function; for dynamics, we discuss models that have transformed our understanding of how beta- band (15-30 Hz) oscillations arise in the parkinsonian basal ganglia.
    [Show full text]
  • Vasopressors and Inotropes in Acute Myocardial Infarction Related Cardiogenic Shock: a Systematic Review and Meta-Analysis
    Journal of Clinical Medicine Review Vasopressors and Inotropes in Acute Myocardial Infarction Related Cardiogenic Shock: A Systematic Review and Meta-Analysis 1, 2, 1 3 Mina Karami y , Veemal V. Hemradj y, Dagmar M. Ouweneel , Corstiaan A. den Uil , Jacqueline Limpens 4, Luuk C. Otterspoor 5, Alexander P. Vlaar 6 , Wim K. Lagrand 6 and José P. S. Henriques 1,* 1 Heart Center, Department of Interventional Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] (M.K.); [email protected] (D.M.O.) 2 Department of Cardiology, Isala, 8025 AB Zwolle, The Netherlands; [email protected] 3 Departments of Cardiology and Intensive Care Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands; [email protected] 4 Medical Library, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] 5 Heart Center Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; [email protected] 6 Department of Intensive Care, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] (A.P.V.); [email protected] (W.K.L.) * Correspondence: [email protected] These two authors contributed equally. y Received: 5 May 2020; Accepted: 25 June 2020; Published: 30 June 2020 Abstract: Vasopressors and inotropes are routinely used in acute myocardial infarction (AMI) related cardiogenic shock (CS) to improve hemodynamics. We aimed to investigate the effect of routinely used vasopressor and inotropes on mortality in AMI related CS. A systematic search of MEDLINE, EMBASE and CENTRAL was performed up to 20 February 2019.
    [Show full text]