DOCSLIB.ORG

Determining Face, Predictive, Construct Validity and Novel Receptor Targets in a Spontaneous Compulsive-Like Mouse Model

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Determining Face, Predictive, Construct Validity and Novel Receptor Targets in a Spontaneous Compulsive-Like Mouse Model Determining face, predictive, construct validity and novel receptor targets in a spontaneous compulsive-like mouse model Item Type Thesis Authors Mitra, Swarup Download date 10/10/2021 23:13:18 Link to Item http://hdl.handle.net/11122/7895 DETERMINING FACE, PREDICTIVE, CONSTRUCT VALIDITY AND NOVEL RECEPTOR TARGETS IN A SPONTANEOUS COMPULSIVE-LIKE MOUSE MODEL By Swarup Mitra, B.S, M.S A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biochemistry and Neuroscience University of Alaska Fairbanks August 2017 APPROVED: Abel Bult-Ito, Committee Chair Kelly Drew, Committee Member Lawrence K. Duffy, Committee Member Kriya Dunlap, Committee Member Thomas Green, Chair Department of Chemistry and Biochemistry Paul Layer, Dean College of Natural Science and Mathematics Michael Castellini, Dean of the Graduate School Abstract Obsessive-compulsive disorder (OCD) is one of the most prevalent neuropsychiatric disorders with no known etiology. Genetic variation, sex differences and physiological stages, such as pregnancy, postpartum and menopause in females, are important factors that are thought to modulate the pathophysiology of the disorder. Deeper understanding of these factors and their role in modulating behaviors is essential to unraveling the complex clinical heterogeneity of OCD. Using a novel mouse model that exhibits a spontaneous compulsive-like phenotype, I investigated the role of strain differences, sex differences, ovarian sex hormones and postpartum lactation in influencing compulsive-like and affective behaviors. Due to the lack of definite neural substrates and first line therapeutic options for treatment resistant patients, I also probed into the role of positive allosteric modulation of nicotinic acetylcholine receptor subtype as a therapeutic target for translational prospects. The thesis showed several significant and novel findings. Strain and sex comparisons of the compulsive-like mouse strains (BIG1 and BIG2) showed that the behavioral outcomes and HPA axis response can be influenced by sex, genotype and sex by genotype interactions. Acute ovariectomy and behavioral assessments after one week, which mimics surgical menopause in humans, increased the compulsive-like behaviors in the BIG strains only. Acute ovariectomy also exacerbated anxiety-like behaviors in the compulsive-like BIG strains. This exacerbation of compulsive-like behaviors was restored only by estrogen and not progesterone, while estrogen and progesterone both restored anxiety­ like behaviors based on the strain and the type of behavioral assessments. Lactating postpartum compulsive-like female mice were protected against compulsive-like behaviors and showed enhanced responsiveness to selective serotonin reuptake inhibitors (SSRIs) compared to the non-lactating and the nulliparous females. Finally, acute and chronic administration of desformylflustrabromine (dFBr), a positive allosteric modulator of a4p2 nicotinic acetylcholine receptors, resulted in the attenuation of compulsive-like behaviors in the mouse model, while iii not affecting anxiety-like behaviors. The current thesis work therefore provides a foundation for further exploration of factors like strain, sex, physiological status and cholinergic receptor subtypes in mouse models to understand the neurobiology and behavioral correlates of OCD in humans. iv Table of Contents Page Title Page............................................................................................................................................. i Abstract................................................................................................................................................iii Table of Contents .................................................................................................................................v List of Figures....................................................................................................................................xv Acknowledgements ..........................................................................................................................xvii Chapter 1: Overview and Research Aims ..........................................................................................1 1.1 Background .............................................................................................................................. 1 1.1.1 Obsessive-Compulsive Disorder ...................................................................................... 1 1.1.2 Clinical Heterogeneity of OCD .......................................................................................... 2 1.1.3 Etiology and Pathophysiology of OCD ..............................................................................4 1.1.3.1 Environmental and Genetic Factors ...........................................................................4 1.1.3.2 Neural Basis: Circuits and Function ...........................................................................5 1.1.3.3 Neurochemistry of OCD..............................................................................................6 1.1.4 Current Treatment Strategies ..........................................................................................11 1.1.4.1 Pharmacotherapy ...................................................................................................... 11 1.1.4.2 Non-Pharmacological Therapies .............................................................................. 13 1.1.5 Animal Models of OCD .................................................................................................... 14 1.1.5.1 Genetic Models..........................................................................................................15 1.1.5.2 Drug Induced Models ................................................................................................ 18 v 1.1.5.3 Spontaneous Models ................................................................................................ 19 1.2 Research Objectives .............................................................................................................. 22 1.2.1 Aim 1...................................................................................................................................23 1.2.2 Aim II................................................................................................................................. 24 1.2.3 Aim III................................................................................................................................ 25 1.2.4 Aim IV :.............................................................................................................................. 26 1.2.5 Aim V ................................................................................................................................ 28 1.3 References .............................................................................................................................. 29 Chapter 2: Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice ......................................................................................................................... 65 2.1 Abstract....................................................................................................................................65 2.2 Introduction .............................................................................................................................. 67 2.3 Methods ....................................................................................................................................70 2.3.1 M ice .................................................................................................................................70 2.3.1.1 Husbandry ..................................................................................................................70 2.3.1.2 Mouse strains ............................................................................................................ 70 2.3.2. Estrous cycle ...................................................................................................................70 2.3.3 Experimental design ........................................................................................................ 71 2.3.4 Measuring compulsive-like behavior ...............................................................................72 2.3.4.1 Nest-building te st ...................................................................................................... 72 2.3.4.2 Marble burying test ....................................................................................................72 2.3.5 Measuring anxiety-like behaviors ................................................................................... 72 vi 2.3.5.1 Open field test ........................................................................................................... 72 2.3.5.2 Elevated plus maze ...................................................................................................73 2.3.6 Measuring novel object recognition behavior ................................................................. 73 2.3.7 Measuring depression-like behavior ............................................................................... 74 2.3.8 Corticosterone ELISA .....................................................................................................
Load more

Recommended publications
  • Datasheet Inhibitors / Agonists / Screening Libraries a DRUG SCREENING EXPERT
    Datasheet Inhibitors / Agonists / Screening Libraries A DRUG SCREENING EXPERT Product Name : Desformylflustrabromine hydrochloride Catalog Number : T11004 CAS Number : 951322-11-5 Molecular Formula : C16H22BrClN2 Molecular Weight : 357.72 Description: Desformylflustrabromine hydrochloride is a selective agonist of nicotinic acetylcholine receptor (nAChR) in α4β2 neurons, with pEC50 of 6.48. Storage: 2 years -80°C in solvent; 3 years -20°C powder; DMSO 105 mg/mL (293.53 mM) Solubility H2O 5 mg/mL (13.98 mM), Need ultrasonic ( < 1 mg/ml refers to the product slightly soluble or insoluble ) Receptor (IC50) α4β2 nAChR In vitro Activity Deformyl fluorobromobromide hydrochloride is a selective agonist of nicotinic acetylcholine receptor (nAChR) in α4β2 neurons, with a pEC50 of 6.48. In high-sensitivity (HS) and low-sensitivity (LS) isomer preparations, norformyl fluoroethyl bromide hydrochloride can enhance and inhibit the current induced by ACh, although compared to the HS isomer, the deformyl hydrochloride Fluoroethyl bromide hydrochloride has a higher effect on the LS isomer (pEC50 = 6.4 ± 0.2) (pEC 50 = 5.6 ± 0.2). Norformyl fluoride ethyl bromide hydrochloride can maximize the response induced by ACh using wild-type receptor expressed by HS isoform preparation, up to 350±20%, which is the same as that received by LS isoform preparation. The body (350±30%) is similar. Reference 1. Nadezhda German, et al. Deconstruction of the α4β2 Nicotinic Acetylchloine (nACh) Receptor Positive Allosteric Modulator des-Formylflustrabromine (dFBr). J Med Chem. 2011 Oct 27;54(20):7259-67. 2. Weltzin MM, et al. Desformylflustrabromine Modulates α4β2 Neuronal Nicotinic Acetylcholine Receptor High- and Low- Sensitivity Isoforms at Allosteric Clefts Containing the β2 Subunit.
    [Show full text]
  • Download PDF Version- Volume 12, July 2012
    Volume 11, July 2012 History of Enrichment in the ILAR Guide for the Care and Use of Laboratory Animals • Drivers for Enrichment in Directive 2010/63/EU • Using Enrichment to Improve Welfare & Reduce Suffering • Tailoring Enrichment to GA Mice • Enrichment and Cephalopods • Evaluating Enrichment is Essential • Reporting Enrichment in Research Papers Volume 12, July 2012 THE Publisher:Global Research Education and Training, LLC Email: [email protected] RECORD Website: http://enrichmentrecord.com A GLOBAL VIEW OF ENVIRONMENTAL ENRICHMENT 4 SPRING 2010 | ENRICHMENTRECORD.COM www.vetbiotech.com IN THIS ISSUE SUMMER 2012 THE RECORD 2 In Other Words Call for Proposals 5 EDITORIAL BOARD Tim Allen, M.S. 7 Animal Welfare Information Center Upcoming Meetings Genevieve Andrews-Kelly, B.S., LATG Huntingdon Life Sciences History of Enrichment in the ILAR 10 Guide for the Care and Use of Laboratory Animals Elizabeth Dodemaide, B.V.Sc., M.A., MACVSc Associate Director, Laboratory Animal Services Rutgers, The State University of New Jersey Drivers for Enrichment in Directive 2010/63/EU 13 Karen Froberg-Fejko, V.M.D., President, Bio-Serv Joanne Gere, Founder, BioScience Collaborative Using Enrichment to Improve Welfare & Reduce Suffering 16 G. Scott Lett, Ph.D., CEO, The BioAnalytics Group LLC Jayne Mackta Tailoring Enrichment in GA Mice 20 President & CEO, Global Research Education & Training LLC Emily G. Patterson-Kane, Ph.D. Enrichment and Cephalopods 24 American Veterinary Medical Association (AVMA) Animal Welfare Division 29 Kathleen L. Smiler, D.V.M., DACLAM Evaluating Enrichment is Essential Consultant, Laboratory Animal Medicine Rhoda Weiner, Weiner & Associates Resources 33 Joanne Zurlo, Ph.D. Director of Science Strategy The Center for Alternatives to Animal Testing (CAAT) Reporting Enrichment in Research Papers 34 Please direct all inquiries to Enriching Profile 36 Rhoda Weiner, Editor: [email protected] 38 We’d loVE TO HEAR FROM YOU! Meeting up We welcome your comments, observations and contributions to The Enrichment Record.
    [Show full text]
  • Conversations with a Neuron, Vol. 2
    ii EDITOR IN CHIEF Sydney Wolfe SUPERVISING STAFF Allison Coffin, PhD Dale Fortin, PhD ii PREFACE III NEWS AND VIEWS PART ONE: NEUROANATOMY ⋙ Adventurous monkeys: choosing to explore the unknown 1 ⋙ Cerebellum at a junction, now there’s a function 4 ⋙ Is your corpus callosum normal? 6 ⋙ The power of music on the brain 9 ⋙ Caffeine: Does it improve our reading skills? 12 ⋙ Neurons in the dorsomedial striatum play a critical role in excessive alcohol consumption 15 ⋙ Predicting nausea using AI 17 ⋙ New imaging technique for assessing damage to brain cells 20 ⋙ Opening the blood brain barrier 23 ⋙ Can’t sleep? You might need some stimulation 25 ⋙ Mutation in receptors of the corpus callosum causes developmental issues in children 28 ⋙ PTSD and its effects on the amygdala and the anterior cingulate cortex 30 ⋙ Broccoli can prevent psychosis 33 ⋙ Size does matter 36 ⋙ Apathy or empathy: the systems behind guilt analyzed 40 ⋙ The obesity epidemic: one more reason to be anxious 43 ⋙ A drug-free solution 46 ⋙ Levels of blood proteins within the brain may be linked to major depressive disorder 49 ⋙ A new target for depression treatment 52 PART TWO: NEUROPHYSIOLOGY ⋙ The “hunt” for an answer continues 55 ⋙ Gene mutation heals traumatic brain injury 57 ⋙ A study of neuronal distribution within the brain of epileptic patients shows the preservation 60 of a certain neuron ⋙ Gene therapy for epilepsy 63 ⋙ Therapeutic potential of taurine supplementation for multiple sclerosis 65 i ⋙ Brevican: perineuronal net protein captures new insights on interneuron
    [Show full text]
  • Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector MINI REVIEW published: 25 November 2015 doi: 10.3389/fnmol.2015.00071 Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation Tasnim S. Mohamed 1, Selwyn S. Jayakar 2 and Ayman K. Hamouda 1,3* 1 Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M Health Sciences Center, Kingsville, TX, USA, 2 Department of Neurobiology, Harvard Medical School, Boston, MA, USA, 3 Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Sciences Center, Bryan, TX, USA Nicotine addiction, the result of tobacco use, leads to over six million premature deaths world-wide per year, a number that is expected to increase by a third within the next two decades. While more than half of smokers want and attempt to quit, only a small percentage of smokers are able to quit without pharmacological interventions. Therefore, over the past decades, researchers in academia and the pharmaceutical industry have focused their attention on the development of more effective smoking cessation therapies, which is now a growing 1.9 billion dollar market. Because the role of neuronal nicotinic acetylcholine receptors (nAChR) in nicotine addiction is well established, nAChR based therapeutics remain the leading strategy for smoking cessation. However, the development of neuronal nAChR drugs that are selective for a nAChR subpopulation is challenging, and only few neuronal nAChR drugs are clinically available. Among the many neuronal nAChR subtypes that have been identified in the brain, the a4b2 subtype is the most abundant and plays a critical role in nicotine addiction.
    [Show full text]
  • Pharmacological Evaluation of Choline on Α4β2 Neuronal Nicotinic Acetylcholine Receptors
    COPYRIGHT AND USE OF THIS THESIS This thesis must be used in accordance with the provisions of the Copyright Act 1968. Reproduction of material protected by copyright may be an infringement of copyright and copyright owners may be entitled to take legal action against persons who infringe their copyright. Section 51 (2) of the Copyright Act permits an authorized officer of a university library or archives to provide a copy (by communication or otherwise) of an unpublished thesis kept in the library or archives, to a person who satisfies the authorized officer that he or she requires the reproduction for the purposes of research or study. The Copyright Act grants the creator of a work a number of moral rights, specifically the right of attribution, the right against false attribution and the right of integrity. You may infringe the author’s moral rights if you: - fail to acknowledge the author of this thesis if you quote sections from the work - attribute this thesis to another author - subject this thesis to derogatory treatment which may prejudice the author’s reputation For further information contact the University’s Copyright Service. sydney.edu.au/copyright Pharmacological Evaluation of Choline on α4β2 Neuronal Nicotinic Acetylcholine Receptors Ladislas Bizimana A thesis submitted in fulfilment of the requirements for the degree of Master of Philosophy Faculty of Pharmacy The University of Sydney 2015 Declaration The work described in this thesis was conducted under the supervision of Dr Thomas Balle and Prof. Mary Collins (Faculty of Pharmacy, The University of Sydney, Sydney). This thesis was edited by Cherry Russell, PhD, retired Associate Professor, Faculty of Health Sciences, The University of Sydney.
    [Show full text]
  • Cannabidiol Reduces Withdrawal Symptoms in Nicotine Dependent Rats Lauren C. Smith,1, 2 Lani Tieu,2 Ray Suhandynata,3 Brent Boom
    Cannabidiol reduces withdrawal symptoms in nicotine dependent rats Lauren C. Smith,1, 2 Lani Tieu,2 Ray Suhandynata,3 Brent Boomhower, 2 Melissa Hoffman,3 "adira Sepulveda,$ Jeremiah D. Momper,$ Robert Fitzgerald,3 Kate Hanham,+ Joseph &owling,+ Marsida Kallupi, *1, 2 and Olivier George., 1, 2 1Department of Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Rd. La ol!a, CA 92037 %Department of Psychiatry, University of Ca!ifornia, San Diego School of Medicine, San Diego, "# 92093 &Department of Pathology, University of Ca!ifornia, San Diego School of Medicine, San Diego, "# 92093 ,Division of Pharmaceutica! Sciences, University of Ca!ifornia, San Diego Skaggs School of Pharmacy and Pharmaceutica! Sciences, La Jol!a, CA 92093 5". Sciences, Inc., 10070 Barnes Canyon Road, San Diego, CA 92121 *Correspondence to: mka!!upi1hea!th.ucsd.edu and olgeorge1hea!th.ucsd.edu 'unding and Disclosure This work was supported by the Nationa! Institute on Drug Abuse (grant no. 1F31D#047113-01 to L.C.S.), Nationa! Institute on A!cohol Abuse and A!coholism (grant no. ##022977 and A#006420 to O.G.), Tobacco-Re!ated Disease Research Program (grant no. 27IR-0047 to O.G.), Tobacco-Re!ated Disease Research Program (grant no. T31KT1859 to 1 +.K.) and CV science (9.G.). Joseph Dow!ing and Kate Hanham are CE9 and Acting Sr. VP of Deve!opment of C. Sciences, Inc. The authors would like to thank Mol!y Brennan, Sharona Sedighim, Liese!ot Carrete, Hassiba Be!djoud and Nathan Ve!arde for providing he!p with the study. /uthor Contributions +;, O:, K=, and JD designed the experimentA LCS and LT performed the behaviora! experiments, nicotine and cotinine blood extraction.
    [Show full text]
  • Pain Research Product Guide | Edition 1
    Pain Research Product Guide | Edition 1 Chili plant Capsicum annuum A source of Capsaicin Contents by Research Area: • Nociception • Ion Channels • G-Protein-Coupled Receptors • Intracellular Signaling Tocris Product Guide Series Pain Research Contents Page Nociception 3 Ion Channels 4 G-Protein-Coupled Receptors 12 Intracellular Signaling 18 List of Acronyms 21 Related Literature 22 Pain Research Products 23 Further Reading 34 Introduction Pain is a major public health problem with studies suggesting one fifth of the general population in both the USA and Europe are affected by long term pain. The International Association for the Study of Pain (IASP) defines pain as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. Management of chronic pain in the clinic has seen only limited progress in recent decades. Treatment of pain has been reliant on, and is still dominated by two classical medications: opioids and non-steroidal anti-inflammatory drugs (NSAIDs). However, side effects such as dependence associated with opioids and gastric ulceration associated with NSAIDs demonstrates the need for new drug targets and novel compounds that will bring in a new era of pain therapeutics. Pain has been classified into three major types: nociceptive pain, inflammatory pain and neuropathic or pathological pain. Nociceptive pain involves the transduction of painful stimuli by peripheral sensory nerve fibers called nociceptors. Neuropathic pain results from damage or disease affecting the sensory system, and inflammatory pain represents the immunological response to injury through inflammatory mediators that contribute to pain. Our latest pain research guide focuses on nociception and the transduction of pain to the spinal cord, examining some of the main classical targets as well as emerging pain targets.
    [Show full text]
  • The Effect of a 5-Ht2a Inverse Agonist on Animal Models Of
    THE EFFECT OF A 5-HT2A INVERSE AGONIST ON ANIMAL MODELS OF OBSESSIVE-COMPULSIVE DISORDER: MARBLE BURYING TASKS by Leah Jorewicz, B.S. THESIS Presented to the Faculty of The University of Houston-Clear Lake In Partial Fulfillment Of the Requirements For the Degree MASTER OF PSYCHOLOGY in Behavioral Neuroscience THE UNIVERSITY OF HOUSTON-CLEAR LAKE MAY, 2018 THE EFFECT OF A 5-HT2A INVERSE AGONIST ON ANIMAL MODELS OF OBSESSIVE-COMPULSIVE DISORDER: MARBLE BURYING TASKS by Leah Jorewicz APPROVED BY __________________________________________ David H. Malin, Ph.D., Chair __________________________________________ Christopher P. Ward, Ph.D., Committee Member APPROVED/RECEIVED BY THE COLLEGE OF HUMAN SCIENCES AND HUMANITIES Samuel Gladden, Ph.D., Associate Dean __________________________________________ Rick Short, Ph.D., Dean Dedication For my mother and father, who always pushed me to always strive to be the best you can be. For not only raising me believing education was the biggest privilege for self- betterment, but also that no matter where you start, you can always improve. I owe all my love for knowledge to them. Acknowledgments I would personally like to thank Dr. Cristopher P. Ward and Dr. David. H. Malin for all that they have taught me through my course of graduate school. It was a hard progress, but they helped me get through it. A special appreciation for both of them taking extra hours outside of office hours to help me because of my work schedule. I would not have been able to complete my degree without that extra help. My thesis would not have been a success if it wasn’t for the amazing classmates I had helping me.
    [Show full text]
  • Botulinum Toxin
    Botulinum toxin From Wikipedia, the free encyclopedia Jump to: navigation, search Botulinum toxin Clinical data Pregnancy ? cat. Legal status Rx-Only (US) Routes IM (approved),SC, intradermal, into glands Identifiers CAS number 93384-43-1 = ATC code M03AX01 PubChem CID 5485225 DrugBank DB00042 Chemical data Formula C6760H10447N1743O2010S32 Mol. mass 149.322,3223 kDa (what is this?) (verify) Bontoxilysin Identifiers EC number 3.4.24.69 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / EGO [show]Search Botulinum toxin is a protein and neurotoxin produced by the bacterium Clostridium botulinum. Botulinum toxin can cause botulism, a serious and life-threatening illness in humans and animals.[1][2] When introduced intravenously in monkeys, type A (Botox Cosmetic) of the toxin [citation exhibits an LD50 of 40–56 ng, type C1 around 32 ng, type D 3200 ng, and type E 88 ng needed]; these are some of the most potent neurotoxins known.[3] Popularly known by one of its trade names, Botox, it is used for various cosmetic and medical procedures. Botulinum can be absorbed from eyes, mucous membranes, respiratory tract or non-intact skin.[4] Contents [show] [edit] History Justinus Kerner described botulinum toxin as a "sausage poison" and "fatty poison",[5] because the bacterium that produces the toxin often caused poisoning by growing in improperly handled or prepared meat products. It was Kerner, a physician, who first conceived a possible therapeutic use of botulinum toxin and coined the name botulism (from Latin botulus meaning "sausage").
    [Show full text]
  • University of Alaska Fairbanks Department of Chemistry & Biochemistry
    AlasChemist University of Alaska Fairbanks Department of Chemistry & Biochemistry June 2011 Volume 29 A Note From The Department Chair This is my first year as the chair of We began a new search for a In May 2011, we held a departmental the Department of Chemistry and biochemist, joint with the Institute of retreat, facilitated by former Provost, Biochemistry, and I'm excited about Arctic Biology, and that search Dean, and Department Chair Paul what we have done as well as grateful continues this summer. Reichardt. The retreat helped us to for the positive efforts of faculty and understand better our current staff at making the department a great We made major changes to our department state and where we want place. The help of past chairs, John department website, increasing to be in the next years. I think it was Keller and Tom Clausen, has been information that we put forward and a great success in identifying where instrumental in surviving this first allowing students to express interest to focus efforts. year. I truly am grateful to them. in our programs through an online system, which we hope will help Sadly for the department, Tom recruiting efforts. We also sought to Clausen is going to be retiring in highlight research efforts and summer 2011. We will miss his successes of the department. We contributions to all areas of the have been trying to serve students department but look forward to better by streamlining the laboratory seeing him around often in the future. sections of general chemistry, We conducted a search for an organic allowing students to register for any chemist and hired Dr.
    [Show full text]
  • Synthesis of Novel Allosteric Agonists and Allosteric Modulators for Nicotinic Acetylcholine Receptors
    Synthesis of Novel Allosteric Agonists and Allosteric Modulators for Nicotinic Acetylcholine Receptors A dissertation presented by Persis Dhankher Supervisor: Dr. Tom Sheppard [November 2013] in partial fulfilment of the requirements for the award of the degree of DOCTOR OF PHILOSOPHY at UNIVERSITY COLLEGE LONDON Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street WC1H 0AJ London Declaration I, Persis Dhankher, confirm that the work presented in this thesis is my own. Where information is derived from other sources, I confirm that it has been indicated and acknowledged. ………………………………. 2 Contents Declaration Abstract Contents Abbreviations Acknowledgements Chapter 1 ................................................................................................................................ 11 Introduction ...................................................................................................................... 11 1.1 Nicotinic Acetylcholine Receptors ...................................................................... 11 1.2 Structure and Function of nAChRs ................................................................... 13 1.2.1 Subunit Subtypes ........................................................................................... 13 1.2.2 Subunit structure of nAChRs ......................................................................... 14 1.3 Heteromeric and Homomeric Receptors ........................................................... 14 1.4 . Orthosteric and
    [Show full text]
  • Marfa, Texas Fourth Annual Translational Neuroscience Meeting October 18Th and 19Th 2018 Research Retreat Expanding Frontiers In
    Department of Pharmacology & Neuroscience Research Retreat Fourth Annual Translational Neuroscience Meeting Expanding frontiers in translational neuroscience October 18th and 19th 2018 Marfa, Texas Department of Pharmacology and Neuroscience October 10th, 2018 Welcome to the fourth annual Research Retreat of the Department of Pharmacology and Neuroscience in Marfa, TX. Our departmental research retreat continues to provide a unique opportunity for professional development through collegial interactions to inform about research accomplishments and ongoing scholarly activities of our department members, discuss and develop new collaborative research projects and grant applications, and reflect on our academic mission in the generation and dissemination of knowledge. We are excited to welcome two distinguished guests to our retreat. Dr. Kathryn Cunningham, Professor and Vice Chair in the Department of Pharmacology & Toxicology and Director of the Center for Addiction Research at UTMB Galveston, is a world leader in translational research and education on substance use disorders and related neuropsychiatric conditions. Dr. Quentin Smith, Professor and Dean of the School of Pharmacy at TTUHSC, has been named Senior Vice President of Research and is overseeing many exciting new initiatives and continued growth of the TTUHSC research enterprise. We look very much forward to their presentations and valuable feedback. This has been a very successful year for our department with several new federal and foundation grant awards and important contributions to medical and graduate education. We are very grateful for the continued support from the offices of the Dean of the School of Medicine and the Sr. VP of Research. I would also like to take this opportunity to thank our staff for their invaluable help and support.
    [Show full text]