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Effects of Stress-Induced Depression on Parkinson's Disease
Effects of stress-induced depression on Parkinson’s disease symptomatology A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Ph.D.) in the Graduate Program in Neuroscience of the College of Medicine 2011 By Ann Marie Hemmerle B.S., University of Dayton Advisor: Kim B. Seroogy, Ph.D. Committee Chair: Neil Richtand, M.D., Ph.D. James P. Herman, Ph.D. Kathy Steece-Collier, Ph.D. Aaron Johnson, Ph.D. Abstract Parkinson’s disease (PD) is a chronic neurodegenerative disorder that primarily affects dopaminergic neurons of the nigrostriatal pathway resulting in debilitating motor symptoms. Parkinson’s patients also have a high risk of comorbid depression, though this aspect of the disorder is less well studied. Understanding the underlying pathology of the comorbidity is important in improving clinical treatments and the quality of life for PD patients. To address this issue, we have developed a new model combining the unilateral striatal 6-hydroxydopamine lesion model of PD with the chronic variable stress model (CVS) of depression. Dysfunction of the hypothalamic-pituitary-adrenal axis and its relationship to depression symptomatology is well established. Stress dysfunction may also have a role in the etiology of preclinical PD non- motor symptoms, and later in the course of the disease, may worsen motor symptoms. The combined model allows us to test the hypothesis that experimental depression exacerbates PD symptoms and to ascertain the mechanisms behind the increased neuronal loss. In the first study, we examined several temporal paradigms of the combined model. -
Brain Imaging
Publications · Brochures Brain Imaging A Technologist’s Guide Produced with the kind Support of Editors Fragoso Costa, Pedro (Oldenburg) Santos, Andrea (Lisbon) Vidovič, Borut (Munich) Contributors Arbizu Lostao, Javier Pagani, Marco Barthel, Henryk Payoux, Pierre Boehm, Torsten Pepe, Giovanna Calapaquí-Terán, Adriana Peștean, Claudiu Delgado-Bolton, Roberto Sabri, Osama Garibotto, Valentina Sočan, Aljaž Grmek, Marko Sousa, Eva Hackett, Elizabeth Testanera, Giorgio Hoffmann, Karl Titus Tiepolt, Solveig Law, Ian van de Giessen, Elsmarieke Lucena, Filipa Vaz, Tânia Morbelli, Silvia Werner, Peter Contents Foreword 4 Introduction 5 Andrea Santos, Pedro Fragoso Costa Chapter 1 Anatomy, Physiology and Pathology 6 Elsmarieke van de Giessen, Silvia Morbelli and Pierre Payoux Chapter 2 Tracers for Brain Imaging 12 Aljaz Socan Chapter 3 SPECT and SPECT/CT in Oncological Brain Imaging (*) 26 Elizabeth C. Hackett Chapter 4 Imaging in Oncological Brain Diseases: PET/CT 33 EANM Giorgio Testanera and Giovanna Pepe Chapter 5 Imaging in Neurological and Vascular Brain Diseases (SPECT and SPECT/CT) 54 Filipa Lucena, Eva Sousa and Tânia F. Vaz Chapter 6 Imaging in Neurological and Vascular Brain Diseases (PET/CT) 72 Ian Law, Valentina Garibotto and Marco Pagani Chapter 7 PET/CT in Radiotherapy Planning of Brain Tumours 92 Roberto Delgado-Bolton, Adriana K. Calapaquí-Terán and Javier Arbizu Chapter 8 PET/MRI for Brain Imaging 100 Peter Werner, Torsten Boehm, Solveig Tiepolt, Henryk Barthel, Karl T. Hoffmann and Osama Sabri Chapter 9 Brain Death 110 Marko Grmek Chapter 10 Health Care in Patients with Neurological Disorders 116 Claudiu Peștean Imprint 126 n accordance with the Austrian Eco-Label for printed matters. -
Personalized Treatment of Alcohol Dependence
Curr Psychiatry Rep DOI 10.1007/s11920-012-0296-5 SUBSTANCE USE AND RELATED DISORDERS (JR MCKAY, SECTION EDITOR) Personalized Treatment of Alcohol Dependence Henry R. Kranzler & James R. McKay # Springer Science+Business Media, LLC 2012 Abstract Pharmacogenetic and adaptive treatment approaches Ondansetron . Sertraline . Adaptive trial designs . can be used to personalize care for alcohol-dependent patients. Adaptive protocol . Stepped care . Treatment algorithm Preliminary evidence shows that variation in the gene encoding the μ-opioid receptor moderates the response to naltrexone when used to treat alcohol dependence. Studies have also shown moderating effects of variation in the gene encoding Introduction the serotonin transporter on response to serotonergic treatment of alcohol dependence. Adaptive algorithms that modify alco- Traditionally, diagnostic tests and medical treatments have hol treatment based on patients’ progress have also shown been developed and evaluated using group data, a “one-size promise. Initial response to outpatient treatment appears to be fits all” approach that leaves little room for individual variation a particularly important in the selection of optimal continuing [1]. Personalized medicine, which uses individual features to care interventions. In addition, stepped-care algorithms can diagnose and treat disease, is of growing interest, having reduce the cost and burden of treatment while maintaining good produced notable successes in oncology and cardiology [2•, outcomes. Finally, matching treatment to specific problems 3]. To date, there have been fewer advances in the personalized present at intake or that emerge during treatment can also diagnosis and treatment of addictive disorders. However, on- improve outcomes. Although all of these effects require repli- going developments in genetics and pharmacogenetics and in cation and further refinement, the future of personalized care for the use of adaptive trial designs offer great potential to extend alcohol dependence appears bright. -
A Nonlinear Relationship Between Cerebral Serotonin Transporter And
The Journal of Neuroscience, March 3, 2010 • 30(9):3391–3397 • 3391 Cellular/Molecular A Nonlinear Relationship between Cerebral Serotonin Transporter and 5-HT2A Receptor Binding: An In Vivo Molecular Imaging Study in Humans David Erritzoe,1,3 Klaus Holst,3,4 Vibe G. Frokjaer,1,3 Cecilie L. Licht,1,3 Jan Kalbitzer,1,3 Finn Å. Nielsen,3,5 Claus Svarer,1,3 Jacob Madsen,2 and Gitte M. Knudsen1,3 1Neurobiology Research Unit and 2PET and Cyclotron Unit, University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark, 3Center for Integrated Molecular Brain Imaging, DK-2100 Copenhagen, Denmark, 4Department of Biostatistics, University of Copenhagen, DK-2200 Copenhagen, Denmark, and 5DTU Informatics, Technical University of Denmark, DK-2800 Lyngby, Denmark Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Withintheserotonintransmittersystem,boththepostsynapticallylocatedserotonin2A(5-HT2A )receptorandthepresynapticserotonin transporter (SERT) are sensitive to chronic changes in cerebral 5-HT levels. Additionally, experimental studies suggest that alterations in either the 5-HT2A receptor or SERT level can affect the protein level of the counterpart. The aim of this study was to explore the covariation betweencerebral5-HT2A receptorandSERT invivointhesamehealthyhumansubjects.Fifty-sixhealthyhumansubjectswithameanage of 36 Ϯ 19 years were investigated. The SERT binding was imaged with [ 11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)- 18 benzonitrile (DASB) and 5-HT2A receptor binding with [ F]altanserin using positron emission tomography. Within each individual, a regionalintercorrelationforthevariousbrainregionswasseenwithbothmarkers,mostnotablyfor5-HT2A receptorbinding.Aninverted U-shaped relationship between the 5-HT2A receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT2A receptor and the SERT cerebral binding suggests that, within the single individual, each marker has a set point adjusted through a common regulator. -
[18F] Altanserin Bolus Injection in the Canine Brain Using PET Imaging
Pauwelyn et al. BMC Veterinary Research (2019) 15:415 https://doi.org/10.1186/s12917-019-2165-5 RESEARCH ARTICLE Open Access Kinetic analysis of [18F] altanserin bolus injection in the canine brain using PET imaging Glenn Pauwelyn1*† , Lise Vlerick2†, Robrecht Dockx2,3, Jeroen Verhoeven1, Andre Dobbeleir2,5, Tim Bosmans2, Kathelijne Peremans2, Christian Vanhove4, Ingeborgh Polis2 and Filip De Vos1 Abstract 18 Background: Currently, [ F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. 18 Results: The distribution of [ F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. Conclusions: This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5- HT2A receptor in the canine brain. -
Radioactive Isotope* in Clinical Medicine and Research Final Programme & Abstracts Book
AT0200334 Radioactive Isotope* in Clinical Medicine and Research ESHS-AT--0031 25th International Symposium 8-11 January, 2002 Bad Gasiein, Austria Final Programme & Abstracts Book Organized by The Austrian Society of Nuclear Medicine and the Departments of Nuclear Medicine and Biomedical Engineering & Physics, University of Vienna http://www. akh-wien. ac. at/bg2002 Merck - kompetent in der Schilddri Euthyrox Jodthyrox Novothyral •« Jodid Merck Fachinformation siehe Innenteil PLEASE BE AWARE THAT ALL OF THE MISSING PAGES IN THIS DOCUMENT WERE ORIGINALLY BLANK Mi^Jx-T^aoM iiiiiiiiii RADIOACTIVE ISOTOPES in Clinical Medicine and Research 25th International Symposium Bad Gastein Austria 8 to 11 January 2002 Organized by The Austrian Society of Nuclear Medicine (ÖGN) and the Departments of Nuclear Medicine and Biomedical Engineering & Physics, University of Vienna Final Programme & Abstracts Book JODID MERCK 100 ng-Tabletten • Zusammensetzung: 1 Tablette enthält 130,8 ng Kaliumjodid, entsprechend 100 (ig Jod. 84 mg Laktose, Magnesiumstearat Cellulose. Maisstärke. Anwen- dungsgebiete: Behandlung des Jodmangelkropfes bei Neugeborenen und Kindern. Gegenanzeigen: Überempfindlichkeit gegen Jod. Manifeste Schilddrüsenüberfunktion. Latente Schilddrüsen- Überfunktion bei Joddosen über 150 ug/Tag. Schwangerschaft und Stillperiode: Wählend der Schwangerschaft und Stillperiode soll die Jodzufuhr fortgesetzt werden. EUTHYROX 50 u.g, 75 ug, 100 ug, 125 ug. 150 ug-Tabletten • Zusammensetzung: 1 Euthyrox 50ng/75ug/100ug/125ug/150ug-Tablette enthält 50 -
Imaging the Neurochemistry of Alcohol and Substance Abuse
539 NEUROIMAGING CLINICS OF NORTH AMERICA Neuroimag Clin N Am 17 (2007) 539–555 Imaging the Neurochemistry of Alcohol and Substance Abuse Diana Martinez, MDa,*, Jong-Hoon Kim, MDa, John Krystal, MDb, Anissa Abi-Dargham, MDa,c - Cocaine dependence Behavioral correlates of low D2/3 receptor Dopamine D2/3 receptors and dopamine binding potential transmission Alcohol dependence and presynaptic Functional significance of low D2/3 dopamine receptor binding in cocaine Alcohol dependence and the dopamine dependence transporter Behavior and dopamine transmission Serotonin and alcohol dependence Imaging cue-induced craving in cocaine Measures of GABA in alcohol dependence dependence Opioids and alcohol dependence Cocaine dependence and the dopamine - Heroin dependence transporter - Methamphetamine abuse Imaging studies of cocaine dependence - Methylenedioxymethamphetamine and other neurotransmitters (Ecstasy) abuse - Alcohol dependence - Hallucinogens - Dopamine D2/3 receptor and alcohol Summary dependence - References Positron emission tomography (PET) and single we briefly overview the concepts that are needed photon emission computed tomography (SPECT) to interpret these studies. The PET radiotracers use radiotracers to image molecular targets in the most frequently used in substance abuse research human brain. These techniques have been applied are those that label the dopamine type 2/3 (D2/3) over the last decade to study addiction and provide receptors of the striatum, such as the antagonists an important body of knowledge about the neuro- -
Molecular Targeting with Radionuclides: State of the Science*
CONTINUING EDUCATION Molecular Targeting with Radionuclides: State of the Science* Scott H. Britz-Cunningham, MD, PhD; and S. James Adelstein, MD, PhD Joint Program in Nuclear Medicine, Harvard Medical School, and Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts foundly, if not unrecognizably, altered in the not-too-distant Inherent in the application of advances in biomedical science to future. nuclear medicine is the concept of molecular targeting: the in vivo concentration of labeled tracer by a gene, its transcribed WHAT IS MOLECULAR TARGETING? DNA, or its protein product. This mechanism of localization has been and is being exploited for both nuclear imaging and ra- “Molecular targeting” may be defined as the specific dioisotopic therapy. Agents, such as antisense molecules, concentration of a diagnostic tracer or therapeutic agent by aptamers, antibodies, and antibody fragments, can be aimed at virtue of its interaction with a molecular species that is molecular targets. Tumor and nerve cell receptors provide such distinctly present or absent in a disease state. The molecular targets. So do certain cellular physiologic activities, including species in question could be a mutated locus of DNA or its metabolism, hypoxia, proliferation, apoptosis, angiogenesis, re- sponse to infection, and multiple drug resistance. In this article protein or RNA product; a gene product of normal sequence we review the principles of molecular targeting based on radio- and structure, aberrantly expressed in a given tissue; or a isotopic methods and provide examples from the literature. We transcriptionally normal gene product whose structure or discuss applications to imaging and therapy and point out the function has been modified by abnormal RNA splicing or hurdles that must be overcome in bringing molecular targeting posttranslational processing. -
Drug Development in Alzheimer's Disease: the Contribution of PET and SPECT
fphar-07-00088 March 29, 2016 Time: 15:21 # 1 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 31 March 2016 doi: 10.3389/fphar.2016.00088 Drug Development in Alzheimer’s Disease: The Contribution of PET and SPECT Lieven D. Declercq1, Rik Vandenberghe2, Koen Van Laere3, Alfons Verbruggen1 and Guy Bormans1* 1 Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium, 2 Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium, 3 Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium Clinical trials aiming to develop disease-altering drugs for Alzheimer’s disease (AD), a neurodegenerative disorder with devastating consequences, are failing at an alarming rate. Poorly defined inclusion-and outcome criteria, due to a limited amount of objective biomarkers, is one of the major concerns. Non-invasive molecular imaging techniques, positron emission tomography and single photon emission (computed) tomography (PET and SPE(C)T), allow visualization and quantification of a wide variety of (patho)physiological processes and allow early (differential) diagnosis in many disorders. Edited by: Albert D. Windhorst, PET and SPECT have the ability to provide biomarkers that permit spatial assessment VU University Medical Center, of pathophysiological molecular changes and therefore objectively evaluate and follow Netherlands up therapeutic response, especially in the brain. A number of specific PET/SPECT Reviewed by: biomarkers used in support of emerging clinical therapies in AD are discussed in this Bashir M. Rezk, Southern University at New Orleans, review. -
Sustained Recreational Use of Ecstasy Is Associated with Altered
Neuropsychopharmacology (2012) 37, 1465–1473 & 2012 American College of Neuropsychopharmacology. All rights reserved 0893-133X/12 www.neuropsychopharmacology.org Sustained Recreational Use of Ecstasy Is Associated with Altered Pre and Postsynaptic Markers of Serotonin Transmission in Neocortical Areas: A PET Study with [11C]DASB and [11C]MDL 100907 ,1,4 1,4 2 1 1 3 Nina BL Urban* , Ragy R Girgis , Peter S Talbot , Lawrence S Kegeles ,XXu, W Gordon Frankle , Carl L Hart1, Mark Slifstein1, Anissa Abi-Dargham1 and Marc Laruelle1 1 2 Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA; Department of Psychiatry, University 3 of Manchester, Manchester, UK; Department of Psychiatry, University of Pittsburgh, PA, USA 3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT2A receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT2A receptors. Positron emission tomography studies using the SERT ligand 11 11 [ C]DASB and the 5-HT2A receptor ligand [ C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. -
Serotonin Transporter Occupancy with Tcas and Ssris: a PET Study in Patients with Major Depressive Disorder
International Journal of Neuropsychopharmacology (2012), 15, 1167–1172. f CINP 2012 BRIEF REPORT doi:10.1017/S1461145711001945 Serotonin transporter occupancy with TCAs and SSRIs: a PET study in patients with major depressive disorder Johan Lundberg, Mikael Tiger, Mikael Lande´n, Christer Halldin and Lars Farde Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Abstract The aim of the present clinical positron emission tomography study was to examine if the 5-HTT is a common target, both for tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Serotonin transporter (5-HTT) occupancy was estimated during treatment with TCA, SSRI and mirtazapine in 20 patients in remission from depression. The patients were recruited from out-patient units and deemed as responders to antidepressive treatment. The radioligand [11C]MADAM was used to determine the 5-HTT binding potential. The mean 5-HTT occupancy was 67% (range 28–86%). There was no significant difference in 5-HTT occupancy between TCA (n=5) and SSRI (n=14). 5-HTT affinity correlated with the recommended clinical dose. Mirtazapine did not occupy the serotonin transporter. The results support that TCAs and SSRIs have a shared mechanism of action by inhibition of 5-HTT. Received 13 November 2011; Reviewed 7 December 2011; Accepted 7 December 2011; First published online 16 January 2012 Key words: 5-HTT, depression, PET, SSRI, TCA. Introduction Molecular imaging methods such as positron emission tomography (PET) allow for measurement of The era of pharmacological treatment of depression drug binding to target proteins in the human brain. began with the tricyclic antidepressant (TCA), Recent advancements include the development of the imipramine, which was found to be effective in the radioligand [11C]DASB, for selective imaging of 5-HTT treatment of endogenous depression (Kuhn, 1958). -
Gut Microbiota Dysbiosis in Depression and Possible Implications of the Antimicrobial E
Journal of Affective Disorders 208 (2017) 22–32 Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of crossmark antidepressant drugs for antidepressant effectiveness ⁎ Danielle Macedoa,1, , Adriano José Maia Chaves Filhoa,1, Caren Nádia Soares de Sousaa, João Quevedob,c,d,e, Tatiana Barichellob,d,e,f, Hélio Vitoriano Nobre Júniorg, David Freitas de Lucenaa a Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil b Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA c Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA d Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA e Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil f Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil g Laboratory of Bioprospection and Experiments in Yeast (LABEL), Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil ARTICLE INFO ABSTRACT Keywords: Objectives: The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At Antidepressants present, drugs belonging to new classes of antidepressants still have antimicrobial effects.