Nicotinic Cholinergic Receptors in VTA Glutamate Neurons Modulate
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Α7 Nicotinic Receptor Up-Regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease
ORIGINAL CONTRIBUTION ␣7 Nicotinic Receptor Up-regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease Scott E. Counts, PhD; Bin He, MD; Shaoli Che, MD, PhD; Milos D. Ikonomovic, MD; Steven T. DeKosky, MD; Stephen D. Ginsberg, PhD; Elliott J. Mufson, PhD Background: Dysfunction of basocortical cholinergic pro- Participants: Participants were members of the Rush jection neurons of the nucleus basalis (NB) correlates with Religious Orders Study cohort. cognitive deficits in Alzheimer disease (AD). Nucleus ba- Main Outcome Measures: Real-time quantitative poly- salis neurons receive cholinergic inputs and express nico- merase chain reaction was performed to validate micro- tinic acetylcholine receptors (nAChRs) and muscarinic array findings. AChRs (mAChRs), which may regulate NB neuron activ- ity in AD. Although alterations in these AChRs occur in Results: Cholinergic NB neurons displayed a statisti- the AD cortex, there is little information detailing whether cally significant up-regulation of ␣7 nAChR messenger defects in nAChR and mAChR gene expression occur in RNA expression in subjects with mild to moderate AD cholinergic NB neurons during disease progression. compared with those with NCI and MCI (PϽ.001). No differences were found for other nAChR and mAChR sub- types across the cohort. Expression levels of ␣7 nAChRs Objective: To determine whether nAChR and mAChR were inversely associated with Global Cognitive Score and gene expression is altered in cholinergic NB neurons dur- with Mini-Mental State Examination performance. ing the progression of AD. Conclusions: Up-regulation of ␣7 nAChRs may signal Design: Individual NB neurons from subjects diag- a compensatory response to maintain basocortical cho- nosed ante mortem as having no cognitive impairment linergic activity during AD progression. -
Research Article Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed Hipscs To
Hindawi Publishing Corporation Stem Cells International Volume 2013, Article ID 784629, 25 pages http://dx.doi.org/10.1155/2013/784629 Research Article Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny Leonhard Linta,1 Marianne Stockmann,1 Qiong Lin,2 André Lechel,3 Christian Proepper,1 Tobias M. Boeckers,1 Alexander Kleger,3 and Stefan Liebau1 1 InstituteforAnatomyCellBiology,UlmUniversity,Albert-EinsteinAllee11,89081Ulm,Germany 2 Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen, Pauwelstrasse 30, 52074 Aachen, Germany 3 Department of Internal Medicine I, Ulm University, Albert-Einstein Allee 11, 89081 Ulm, Germany Correspondence should be addressed to Alexander Kleger; [email protected] and Stefan Liebau; [email protected] Received 31 January 2013; Accepted 6 March 2013 Academic Editor: Michael Levin Copyright © 2013 Leonhard Linta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. -
Ion Channels
UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. -
Nicotinic Receptor Gene Variants Interact with Attention Deficient
Addictive Behaviors 38 (2013) 2683–2689 Contents lists available at ScienceDirect Addictive Behaviors Nicotinic receptor gene variants interact with attention deficient hyperactive disorder symptoms to predict smoking trajectories from early adolescence to adulthood Chien-Ti Lee a, Bernard F. Fuemmeler a,b,⁎, F. Joseph McClernon c,d, Allison Ashley-Koch e, Scott H. Kollins c a Duke University Medical Center, Department of Psychology Neuroscience, Durham, NC DUMC 104006, Durham, NC 27710, United States b Duke University, Department of Community and Family Medicine, Durham, NC DUMC 104006, Durham, NC 27710, United States c Duke University Medical Center, Department of Psychiatry and Behavioral Science, Durham, NC DUMC 3527, Durham, NC 27710, United States d Durham VAMC Mental Illness Research, Education, and Clinical Center, Durham, NC 508 Fulton Street, Durham, NC 27705, United States e Duke University Medical Center, Center for Human Genomics, DUMC Box 2903, Durham, NC 27710, United States HIGHLIGHTS • Associations between nAChR SNPs, ADHD symptoms, and smoking patterns were examined. • Growth modeling used to identify smoking patterns based on SNP and ADHD symptoms. • ADHD symptom severity predicted the number of cigarettes smoked. • Certain CHRNA6 variants predicted pattern of cigarette use over time. • CHRNB3 variant × ADHD symptom interaction increased risk of cigarette use over time. article info abstract Keywords: Objective: To examine the association of single nucleotide polymorphisms (SNPs) of the CHRNB3 nAChR SNPs (rs13280604) and CHRNA6 (rs892413) nicotinic acetylcholine receptor (nAChR) genes and symptoms of ADHD attention deficit hyperactivity disorder (ADHD) in predicting smoking patterns from early adolescence to Smoking development adulthood. Method: A longitudinal cohort of 1137 unrelated youths from the National Longitudinal Study of Adolescent Health provided responses to four surveys from Waves I to IV, and a genetic sample in Wave III. -
Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence
G C A T T A C G G C A T genes Article Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence Lingjun Zuo 1, Rolando Garcia-Milian 2, Xiaoyun Guo 1,3,4,*, Chunlong Zhong 5,*, Yunlong Tan 6, Zhiren Wang 6, Jijun Wang 3, Xiaoping Wang 7, Longli Kang 8, Lu Lu 9,10, Xiangning Chen 11,12, Chiang-Shan R. Li 1 and Xingguang Luo 1,6,* 1 Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA; [email protected] (L.Z.); [email protected] (C.-S.R.L.) 2 Curriculum & Research Support Department, Cushing/Whitney Medical Library, Yale University School of Medicine, New Haven, CT 06510, USA; [email protected] 3 Shanghai Mental Health Center, Shanghai 200030, China; [email protected] 4 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA 5 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China 6 Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing 100096, China; [email protected] (Y.T.); [email protected] (Z.W.) 7 Department of Neurology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, China; [email protected] 8 Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Diseases of Tibet Autonomous Region, Xizang Minzu University School of Medicine, Xianyang, Shanxi 712082, China; [email protected] 9 Provincial Key Laboratory for Inflammation and Molecular Drug Target, Medical -
Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology
brain sciences Review Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology Andrea Becchetti 1,* , Laura Clara Grandi 1 , Giulia Colombo 1 , Simone Meneghini 1 and Alida Amadeo 2 1 Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy; [email protected] (L.C.G.); [email protected] (G.C.); [email protected] (S.M.) 2 Department of Biosciences, University of Milano, 20133 Milano, Italy; [email protected] * Correspondence: [email protected] Received: 13 October 2020; Accepted: 21 November 2020; Published: 25 November 2020 Abstract: Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na+-gated K+ channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns α4 and β2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant α2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of α2-containing (α2*) nAChRs in the human brain. -
Nicotinic Acetylcholine Receptor Variation and Response to Smoking Cessation Therapies Andrew W
94 Original article Nicotinic acetylcholine receptor variation and response to smoking cessation therapies Andrew W. Bergena, Harold S. Javitza, Ruth Krasnowa, Denise Nishitaa, Martha Michela, David V. Contib, Jinghua Liub, Won Leeb, Christopher K. Edlundb, Sharon Hallc, Pui-Yan Kwokd, Neal L. Benowitze, Timothy B. Bakerf, Rachel F. Tyndaleh, Caryn Lermang and Gary E. Swana Objective To evaluate the association of nicotinic and with increased abstinence in the NRT PG at 6MO acetylcholine receptor (nAChR) single nucleotide [for rs588765, 2.07 (1.11–3.87) and for rs1051730, 2.54 polymorphism (SNP) with 7-day point prevalence (1.29–4.99)]. We observed significant heterogeneity abstinence (abstinence) in randomized clinical trials in rs1051730 effects (F = 2.48, P = 0.021) between PGs. of smoking cessation therapies in individuals grouped Conclusion chr15q25.1 nAChR SNP risk alleles for by pharmacotherapy randomization to inform the smoking heaviness significantly increase relapse with PLA development of personalized smoking cessation therapy. treatment and significantly increase abstinence with NRT. Materials and methods We quantified association of four These SNP–PG associations require replication SNPs at three nAChRs with abstinence in eight randomized in independent samples for validation, and testing in larger clinical trials. Participants were 2633 outpatient treatment- sample sizes to evaluate whether similar effects occur in seeking, self-identified European ancestry individuals other PGs. Pharmacogenetics and Genomics 23:94–103 c -
Structural Analysis of Pathogenic Missense Mutations in GABRA2 and Identification of a Novel De Novo Variant in the Desensitization Gate
Received: 22 October 2019 | Revised: 29 November 2019 | Accepted: 10 December 2019 DOI: 10.1002/mgg3.1106 ORIGINAL ARTICLE Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate Alba Sanchis-Juan1,2 | Marcia A. Hasenahuer3,4 | James A. Baker3 | Amy McTague5 | Katy Barwick5 | Manju A. Kurian5 | Sofia T. Duarte6 | NIHR BioResource | Keren J. Carss1,2 | Janet Thornton3 | F. Lucy Raymond2,4 1Department of Haematology, University of Cambridge, NHS Blood and Transplant Abstract Centre, Cambridge, UK Background: Cys-loop receptors control neuronal excitability in the brain and their 2NIHR BioResource, Cambridge dysfunction results in numerous neurological disorders. Recently, six missense vari- University Hospitals NHS Foundation ants in GABRA2, a member of this family, have been associated with early infantile Trust, Cambridge Biomedical Campus, Cambridge, UK epileptic encephalopathy (EIEE). We identified a novel de novo missense variant 3European Molecular Biology Laboratory, in GABRA2 in a patient with EIEE and performed protein structural analysis of the European Bioinformatics Institute, seven variants. Wellcome Genome Campus, Hinxton, . Cambridge, UK Methods: The novel variant was identified by trio whole-genome sequencing We 4Department of Medical Genetics, performed protein structural analysis of the seven variants, and compared them to Cambridge Institute for Medical Research, previously reported pathogenic mutations at equivalent positions in other Cys-loop University of Cambridge, Cambridge, UK receptors. Additionally, we studied the distribution of disease-associated variants in 5Developmental Neurosciences, Great the transmembrane helices of these proteins. Ormond Street Institute of Child Health, University College London, London, UK Results: The seven variants are in the transmembrane domain, either close to the de- 6Hospital Dona Estefânia, Centro Hospitalar sensitization gate, the activation gate, or in inter-subunit interfaces. -
The Functional Role of a Human Polymorphism (Rs2304297) in the 3'-UTR of the CHRNA6 Gene in Nicotine-Induced Locomotion and An
Submitter Name: Anjelica Cardenas Submitted email: [email protected] PI Name (if different): Shahrdad Lotfipour, PhD PI email (if different): [email protected] The Functional Role of a Human Polymorphism (rs2304297) in the 3’-UTR of the CHRNA6 Gene in Nicotine-Induced Locomotion and Anxiety in Adolescent Sprague Dawley Rats Anjelica Cardenas1, Yasamin Heydary1, Shahrdad Lotfipour1,2,3 1Pharmaceutical Sciences, University of California, Irvine; 2Emergency Medicine, University of California, Irvine, 3Pathology and Laboratory Medicine, University of California, Irvine A single nucleotide polymorphism (SNP), rs2304297, in the human 3’-untranslated region (UTR) of the alpha(α)6 nicotinic acetylcholine receptor (nAChR) subunit gene (CHRNA6), is associated with enhanced smoking during adolescence in humans. The α6 nAChR subunit exhibits peak expression during adolescence in dopaminergic neurons of the ventral tegmental area and substantia nigra in rodents. Studies using α6 genetic animal models and pharmacological approaches provide evidence that α6-containing (*) nAChRs mediate nicotine-induced locomotor activity, anxiety, and self-administration. To study the role of the human CHRNA6 3’-UTR SNP in vivo, our lab generated a humanized rodent line via CRISPR/Cas9 genomic engineering. Using our new genetic animal model, our current studies test the functional role of the SNP in adolescent locomotor response and anxiety-like behavior following acute and sub-chronic nicotine exposure. We hypothesize that the CHRNA6 SNP will interact with nicotine to enhance locomotion and anxiolytic behavior in male and female humanized 3’-UTR CHRNA6 rats. Our results illustrate sub-chronic, but not acute, nicotine exposure leads to genotype- and sex-dependent enhancement of locomotion. For anxiety-like behavior, we observe genotype-dependent effects for acute nicotine exposure and genotype- and sex-dependent effects for sub-chronic nicotine versus saline exposure. -
Expression of Nicotinic Acetylcholine Receptor Subunit Genes in Non–Small-Cell Lung Cancer Reveals Differences Between Smokers and Nonsmokers
Research Article Expression of Nicotinic Acetylcholine Receptor Subunit Genes in Non–Small-Cell Lung Cancer Reveals Differences between Smokers and Nonsmokers David Chi-leung Lam,1,2 Luc Girard,4 Ruben Ramirez,4 Wing-shun Chau,3 Wai-sing Suen,3 Shelley Sheridan,4 Vicky P.C. Tin,2 Lap-ping Chung,2 Maria P. Wong,2 Jerry W. Shay,5 Adi F. Gazdar,4 Wah-kit Lam,1 and John D. Minna4 Departments of 1Medicine and 2Pathology, University of Hong Kong; 3Cardiothoracic Surgical Unit, The Grantham Hospital, HKSAR, China; and 4Hamon Center for Therapeutic Oncology Research and 5Department of Cell Biology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas Abstract could also participate in lung cancer pathogenesis by activating Nicotine and its derivatives, by binding to nicotinic acetyl- signal transduction pathways such as the Akt pathway (1). One choline receptors (nAChR) on bronchial epithelial cells, can model could be that nicotine by stimulating nicotinic AChRs regulate cellular proliferation and apoptosis via activating the (nAChR) would activate Akt in lung epithelial cells and perhaps Akt pathway. Delineation of nAChR subtypes in non–small-cell stimulate cell proliferation and/or overcome apoptotic responses lung cancers (NSCLC) may provide information for prevention engendered by carcinogen exposure (1). If this model is true, then or therapeutic targeting. Expression of nAChR subunit genes one may ask whether lung tumors have different nAChR expression in 66 resected primary NSCLCs, 7 histologically non-involved patterns compared with normal lung tissues and whether lung lung tissues, 13 NSCLC cell lines, and 6 human bronchial cancers arising in smokers have different patterns compared with epithelial cell lines (HBEC) was analyzed with quantitative never smokers. -
Resequencing of Nicotinic Acetylcholine Receptor Genes and Association of Common and Rare Variants with the Fagerstro¨M Test for Nicotine Dependence
Neuropsychopharmacology (2010) 35, 2392–2402 & 2010 Nature Publishing Group All rights reserved 0893-133X/10 $32.00 www.neuropsychopharmacology.org Resequencing of Nicotinic Acetylcholine Receptor Genes and Association of Common and Rare Variants with the Fagerstro¨m Test for Nicotine Dependence 1,4 1 2 2 1 Jennifer Wessel , Sarah M McDonald , David A Hinds , Renee P Stokowski , Harold S Javitz , 2 1 2 1 2 1 Michael Kennemer , Ruth Krasnow , William Dirks , Jill Hardin , Steven J Pitts , Martha Michel , 1 2 3 1 ,1 Lisa Jack , Dennis G Ballinger , Jennifer B McClure , Gary E Swan and Andrew W Bergen* 1 2 3 Center for Health Sciences, SRI International, Menlo Park, CA, USA; Perlegen Sciences, Mountain View, CA, USA; Group Health Research 4 Institute, Seattle, WA, USA; Department of Public Health, Indiana University School of Medicine, Indianapolis, IN, USA Common single-nucleotide polymorphisms (SNPs) at nicotinic acetylcholine receptor (nAChR) subunit genes have previously been associated with measures of nicotine dependence. We investigated the contribution of common SNPs and rare single-nucleotide variants (SNVs) in nAChR genes to Fagerstro¨m test for nicotine dependence (FTND) scores in treatment-seeking smokers. Exons of 10 genes were resequenced with next-generation sequencing technology in 448 European-American participants of a smoking cessation trial, and CHRNB2 and CHRNA4 were resequenced by Sanger technology to improve sequence coverage. A total of 214 SNP/SNVs were identified, of which 19.2% were excluded from analyses because of reduced completion rate, 73.9% had minor allele frequencies o5%, and 48.1% were novel relative to dbSNP build 129. -
Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells Jie Qian Virginia Commonwealth University
Virginia Commonwealth University VCU Scholars Compass Physiology and Biophysics Publications Dept. of Physiology and Biophysics 2015 Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells Jie Qian Virginia Commonwealth University Shobha K. Mummalaneni Virginia Commonwealth University Reem M. Alkahtan Virginia Commonwealth University See next page for additional authors Follow this and additional works at: http://scholarscompass.vcu.edu/phis_pubs Part of the Medicine and Health Sciences Commons Copyright: © 2016 Qian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Downloaded from http://scholarscompass.vcu.edu/phis_pubs/54 This Article is brought to you for free and open access by the Dept. of Physiology and Biophysics at VCU Scholars Compass. It has been accepted for inclusion in Physiology and Biophysics Publications by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Authors Jie Qian, Shobha K. Mummalaneni, Reem M. Alkahtan, Sunila Mahavadi, Karnam S. Murthy, John R. Grider, and Vijay Lyall This article is available at VCU Scholars Compass: http://scholarscompass.vcu.edu/phis_pubs/54 RESEARCH ARTICLE Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic