DOCSLIB.ORG

Advanced Techniques to Study Anesthetic Effects on the Nervous System

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Advanced Techniques to Study Anesthetic Effects on the Nervous System Global Journal of Anesthesiology eertechz Cheng Wang* Mini Review Division of Neurotoxicology, National Center for Toxicological Research (NCTR)/FDA, Je erson, AR, USA Advanced Techniques to Study Dates: Received: 19 April, 2016; Accepted: 26 April, 2016; Published: 27 April, 2016 Anesthetic E ects on the Nervous *Corresponding author: Cheng Wang, Division of Neurotoxicology, National Center for Toxicological System Research (NCTR)/FDA, Jefferson, AR; USA, E-mail: mitochondrial fusion and ssion with defects corresponding to an www.peertechz.com imbalance in the process that ultimately may lead to cell death [6]. ISSN: 2455-3476 It has been reported that changes in overall mitochondrial shape and number due to a perturbation in the fusion/ ssion process appears Review to accompany inner-membrane remodeling during apoptosis, and administration of anesthetics (e.g., ketamine) signi cantly decreases Recently, there has been increased interest and concern regarding both [7]. the safety of anesthetics on the long-term impairment of the central nervous system (CNS). e eld of anesthesia-related toxicology, Mitochondrial ultrastructure is best studied directly using the therefore, has engaged multiple scienti c disciplines in attempt high resolution a orded by electron microscopy (EM). Although to identify the basic characteristics of the anesthetic agents that transmission electron microscopy (TEM) has been used to produce harmful acute and/or chronic e ects on the nervous system. distinguish inner membrane topologies with some success, one of Currently, the clinical relevance of anesthetic neurotoxicity is an the major drawbacks of conventional TEM is the inability to obtain urgent matter of public health. three-dimensional (3D) information from two-dimensional (2D) micrographs. Recently, a relatively new EM method, serial block-face In the preclinical studies [1,2] it has been demonstrated that, scanning EM (SBF-SEM), has the potential to bridge this gap [8]. at clinically-relevant concentrations, the commonly used general e commercial SBF-SEM system, the Gatan 3View, houses a fully anesthetics including sevo urane, can e ectively induce and maintain automated ultramicrotome within the specimen chamber of a eld a surgical plane of anesthesia in developing nonhuman primates and/ or rodents as evidenced by lack of voluntary movement with reduced emission scanning electron microscope (SEM). Instead of imaging muscle tone and minimal reaction to physical stimulation. ultrathin sections on grids as in TEM, the 3View images the surface of the bulk sample using backscatter electron detection. A er each Signi cant advances have been made in recent years in the scan, the sample block advances and a diamond knife removes a thin techniques (e.g., molecular imaging, calcium imaging, lipidomics and slice of sample (25-200 nm). e freshly cut block face is then imaged, 3D electron microscopy) that have revolutionized our ability to study and the process is repeated. e desired sample depth is in situ, anesthetic neurotoxicity. When combined with the classic/traditional building a stack of aligned SEM images that can be used to generate methods, such as histo-pathological and biochemical assays, these 3D reconstructions of data sets [9]. e data from the control and research approaches make it possible to map and analyze genetic anesthetic SBF-SEM can be modeled with a single statistical equation and complex phenotype variations, morphological and biochemical that allows for di erent intercepts and slopes for the two experimental alterations, and dynamic pathological changes, as well as long-term groups. e model is given by behavioral de cits. ese advanced approaches also enable us to dissect mechanisms that underlie anesthetic-induced neurotoxicity, Vi =α + β SAi + γ I i + δ(*) I SA i + ε i , and to develop potential protective strategies. is editorial provides th examples of how these approaches have been applied to solve where Vi, Ii, and SAi denote the i observation of volume, the major problems induced by inappropriate and/or prolonged treatment indicator with 0=control and 1=anesthetic agent (e.g., ε anesthetic exposure and their underlying mechanisms. ketamine), and surface area, respectively, i is the random error term, and α is the y-intercept. e model reduces toV=α + β SA + ε 3D Electron microscopy to quantify anesthetic- i i i induced mitochondrial defects for the control group. Alternatively, sthe model can be rewritten as V =()()α + γ + β + δSA + ε for the anesthetic group. All data It is known that the mitochondria play a pivotal role in i i i the cell death pathways that are implicated in several types of analysis can be performed using Microso Excel and R (www.r- neurodegeneration [3-5]. Mitochondria form a dynamic network project.org). within the cell; continuously fusing and dividing to meet the Taken together, SBF-SEM may help illuminate the link between metabolic demands of the cell. It has been suggested that the topology inner membrane remodeling and mitochondrial fusion/ ssion; of the inner mitochondrial membrane represents a balance between knowledge of the changes occurring at the mitochondrial level may, Citation: Wang C (2016) Advanced Techniques to Study Anesthetic Effects on the Nervous System. Glob J Anesthesiol 3(1): 007-010. DOI: 10.17352/2455- 3476.000023 007 Wang (2016) therefore, provide important insight into one of the key mechanisms interleukin (IL)-17, macrophage in ammatory protein-1α (MIP-1α), of anesthetic-induced neurotoxicity. epidermal growth factor (EGF), and monokine induced by gamma interferon (MIG) were all signi cantly elevated in the anesthetic Lipidomics analyses to evaluate anesthetic-induced (sevo urane)-exposed animals [1]. us, elevated ROS production neurotoxicity and cytokine secretions could be critical for the development of It is known that the primate brain as an organ contains the largest neuronal damage induced by anesthetics. is was subsequently shown diversity of lipid classes and molecular species, and the largest lipid [1], by an increased number of Fluoro-Jade C-positive neurons, a mass relative to protein in comparison to other organs except adipose marker for neuronal degeneration, in the frontal cortex. Importantly, tissue. e literature on the frequently used general anesthetics sevo urane-induced neuronal damage in the frontal cortex in studies has detailed their e ects on synaptogenesis, synaptic networking, with infant monkeys is consistent with that observed in previous neurogenesis, neural cell death and behavioral de cits. However, rodent studies, indicating sevo urane-induced neurodegenerative there has been limited research evaluating whether and/or how e ects are dependent on delivered concentrations and exposure anesthetic agents a ect lipids, the most abundant component in the duration [2]. erefore, as biomarkers, it is quite possible that the brain, other than water. presence and severity of anesthetic-induced neurotoxicity could e ectively be re ected in speci c alterations in cytokine/chemokine us, identifying biomarkers, especially from samples of secretion and the levels of ROS-mediated polyunsaturated fatty acid brain tissue and blood plasma, may assist in the early detection of peroxidative products, such as 4-hydroxynonenal (HNE) in brain neurotoxic e ects associated with exposure to general anesthetics and tissue, plasma (blood), and cerebral spinal uid. therefore, may prove useful in safety evaluations. Practically, lipid extraction from brain tissue and/or blood can be performed using Calcium imaging to dissect the underlying a modi ed Bligh and Dyer method [10]. For examples, to con rm mechanisms of anesthetic-induced neurotoxicity the identi cation of the subclass of phosphatidylethanolamine It is known that the most frequently used general anesthetics (PE) species, a portion of lipid extract can be derivatized using have either NMDA receptor blocking or GABA receptor enhancing uorenylmethoxycarbonyl (Fmoc) chloride [11]. Precursor ion properties. Noncompetitive antagonism of NMDA receptors is scanning can then be performed to monitor the fatty acid fragments thought to be one of the mechanisms by which anesthetics, e.g., and identify the aliphatic-chains in each of the PE species [12], ketamine, produces its primary therapeutic e ect. It has been reported followed by lipid analyses using a triple-quadrupole mass spectrometer that NMDA receptor NR1 expression in ketamine-exposed brains is equipped with a nanomate automated nanospray device [13]. Diluted signi cantly higher than in controls [19,20]. It has been postulated lipid extract can be directly infused through the nanomate device that this up-regulation of the NMDA receptor is responsible for or [13]. For each mass spectrum a 1-minute period of signal averaging at least contributes to ketamine-induced neurotoxicity because it in the pro le mode is typically employed. Data processing, including allows for a toxic accumulation of intracellular calcium (Ca2+) once ion peak selection, baseline correction, data transfer, peak intensity ketamine is washed out of the system. comparison, 13C de-isotoping, and quantitation is then performed using an in-house programmed Microso Excel macro [12], a er Ca2+ is a vital element in the process of neurotransmitter release, taking into consideration the principles of lipidomics [14]. and is a common signaling molecule. Calcium can act in signal transduction a er in ux resulting from activation of ion channels Lipids play many roles in cellular
Load more

Recommended publications
  • Radiation Dosimetry of the Α4β2 Nicotinic Receptor Ligand (+)-[18F
    Kranz et al. EJNMMI Physics (2016) 3:25 EJNMMI Physics DOI 10.1186/s40658-016-0160-5 ORIGINAL RESEARCH Open Access Radiation dosimetry of the α4β2 nicotinic receptor ligand (+)-[18F]flubatine, comparing preclinical PET/MRI and PET/CT to first-in-human PET/CT results Mathias Kranz1†, Bernhard Sattler2†, Solveig Tiepolt2, Stephan Wilke2, Winnie Deuther-Conrad1, Cornelius K. Donat1,4, Steffen Fischer1, Marianne Patt2, Andreas Schildan2, Jörg Patt2, René Smits3, Alexander Hoepping3, Jörg Steinbach1, Osama Sabri2† and Peter Brust1*† * Correspondence: [email protected] †Equal contributors Abstract 1 Institute of Radiopharmaceutical 18 Cancer Research, Research Site Background: Both enantiomers of [ F]flubatine are new radioligands for neuroimaging Leipzig, Helmholtz-Zentrum of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) Dresden-Rossendorf, exhibiting promising pharmacokinetics which makes them attractive for different clinical Permoserstraße 15, 04318 Leipzig, 18 Germany questions. In a previous preclinical study, the main advantage of (+)-[ F]flubatine 18 Full list of author information is compared to (−)-[ F]flubatine was its higher binding affinity suggesting that available at the end of the article 18 (+)-[ F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (−)-[18F]flubatine in early stages of Alzheimer’s disease. To support the clinical translation, we investigated a fully image-based internal dosimetry approach for (+)-[18F]flubatine, comparing mouse data collected on a preclinical PET/MRI system to piglet and first-in-human data acquired on a clinical PET/CT system. Time-activity curves (TACs) were obtained from the three species, the animal data extrapolated to human scale, exponentially fitted and the organ doses (OD), and effective dose (ED) calculated with OLINDA.
    [Show full text]
  • Acetylcholine Signaling System in Progression of Lung Cancers
    Pharmacology & Therapeutics 194 (2019) 222–254 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Acetylcholine signaling system in progression of lung cancers Jamie R. Friedman a,1, Stephen D. Richbart a,1,JustinC.Merritta,KathleenC.Browna, Nicholas A. Nolan a, Austin T. Akers a, Jamie K. Lau b, Zachary R. Robateau a, Sarah L. Miles a,PiyaliDasguptaa,⁎ a Department of Biomedical Sciences, Joan C. Edwards School of Medicine, 1700 Third Avenue, Huntington, WV 25755 b Biology Department, Center for the Sciences, Box 6931, Radford University, Radford, Virginia 24142 article info abstract Available online 3 October 2018 The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline Keywords: transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyl- Lung cancer transferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetyl- Acetylcholine cholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic Cholinergic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components Proliferation of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend Invasion Anti-cancer drugs is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic ciga- rettes considered by many as a “safe” alternative to smoking.
    [Show full text]
  • Final Opinion on Additives Used in Tobacco Products
    Tobacco Additives II Final Scientific Committee on Health, Environmental and Emerging Risks SCHEER Opinion on Additives used in tobacco products (Opinion 2) Tobacco Additives II The SCHEER approved this Opinion by written procedure on 16 December 2016. 1 Tobacco Additives II Final Opinion About the Scientific Committees (2016-2021) Two independent non-food Scientific Committees provide the Commission with the scientific advice it needs when preparing policy and proposals relating to consumer safety, public health and the environment. The Committees also draw the Commission's attention to the new or emerging problems which may pose an actual or potential threat. They are: the Scientific Committee on Consumer Safety (SCCS) and the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER). The Scientific Committees review and evaluate relevant scientific data and assess potential risks. Each Committee has top independent scientists from all over the world who are committed to work in the public interest. In addition, the Commission relies upon the work of other Union bodies, such as the European Food Safety Authority (EFSA), the European Medicines Agency (EMA), the European Centre for Disease prevention and Control (ECDC) and the European Chemicals Agency (ECHA). SCHEER This Committee, on request of Commission services, provides Opinions on questions concerning health, environmental and emerging risks. The Committees addresses questions on: - health and environmental risks related to pollutants in the environmental media and other biological and physical factors in relation to air quality, water, waste and soils. - complex or multidisciplinary issues requiring a comprehensive assessment of risks to consumer safety or public health, for example antimicrobial resistance, nanotechnologies, medical devices and physical hazards such as noise and electromagnetic fields.
    [Show full text]
  • Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects
    Neuropsychopharmacology (2010) 35, 1485–1499 & 2010 Nature Publishing Group All rights reserved 0893-133X/10 $32.00 www.neuropsychopharmacology.org Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects ,1,2 3 1 1,2 3 Bryon Adinoff* , Michael D Devous Sr , Mark J Williams , Susan E Best , Thomas S Harris , 4 1 1 Abu Minhajuddin , Tanya Zielinski and Munro Cullum 1 2 Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; VA North Texas Health Care System, Dallas, TX, 3 4 USA; Nuclear Medicine Center and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA Changes in the brain’s cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer’s disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (po0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula.
    [Show full text]
  • Nicotinic Filtering of Sensory Processing in Auditory Cortex
    UC Irvine UC Irvine Previously Published Works Title Nicotinic filtering of sensory processing in auditory cortex Permalink https://escholarship.org/uc/item/846470hj Journal Frontiers in Behavioral Neuroscience, 6 ISSN 1662-5153 Authors Metherate, Raju Intskirveli, Irakli Kawai, Hideki D Publication Date 2012-07-19 DOI 10.3389/fnbeh.2012.00044 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California REVIEW ARTICLE published: 19 July 2012 BEHAVIORAL NEUROSCIENCE doi: 10.3389/fnbeh.2012.00044 Nicotinic filtering of sensory processing in auditory cortex Raju Metherate 1*, Irakli Intskirveli 1 and Hideki D. Kawai 2 1 Department of Neurobiology and Behavior, Center for Hearing Research, University of California, Irvine, Irvine, CA, USA 2 Faculty of Engineering, Department of Bioinformatics, Soka University, Hachiouji, Tokyo, Japan Edited by: Although it has been known for decades that the drug nicotine can improve cognitive Anita Disney, Salk Institute for function, the nature of its effects and the underlying mechanisms are not well understood. Biological Studies, USA Nicotine activates nicotinic acetylcholine (ACh) receptors (nAChRs) that normally are Reviewed by: activated by endogenous ACh, presumably “hijacking” the cholinergic contribution to Jean-Marc Edeline, Université de Paris, France multiple cognitive functions, notably attention. Thus, studying nicotine’s effects helps to Alex Thiele, Newcastle University, better understand a commonly used drug as well as functions of nAChRs. Moreover, UK nicotinic agonists are being developed to treat a variety of disorders that involve *Correspondence: attention-related or age-related cognitive dysfunction. Studies have shown that nicotine Raju Metherate, Department of can enhance processing of attended stimuli and/or reduce processing of distracters; Neurobiology and Behavior, Center for Hearing Research, University of that is, nicotine enhances attentional filtering.
    [Show full text]
  • PET Imaging of A4b2* Nicotinic Acetylcholine Receptors: Qualitative Analysis of 18F-Nifene Kinetics in the Nonhuman Primate
    Journal of Nuclear Medicine, published on July 31, 2012 as doi:10.2967/jnumed.112.103846 PET Imaging of a4b2* Nicotinic Acetylcholine Receptors: Qualitative Analysis of 18F-Nifene Kinetics in the Nonhuman Primate Ansel T. Hillmer1,2, Dustin W. Wooten1,2, Maxim S. Slesarev2, Elizabeth O. Ahlers2, Todd E. Barnhart1, Dhanabalan Murali1,2, Mary L. Schneider3, Jogeshwar Mukherjee4, and Bradley T. Christian1,2,5 1Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin; 2Waisman Brain Imaging Laboratory, University of Wisconsin-Madison, Madison, Wisconsin; 3Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin; 4Department of Radiological Sciences, University of California-Irvine, Irvine, California; and 5Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin Key Words: nAChR; PET; nicotine; 18F-nifene; compartment The PET radioligand 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyr- modeling idine (18F-nifene) is an a4b2* nicotinic acetylcholine receptor J Nucl Med 2012; 53:1–10 (nAChR) agonist developed to provide accelerated in vivo equi- DOI: 10.2967/jnumed.112.103846 librium compared with existing a4b2* radioligands. The goal of this work was to analyze the in vivo kinetic properties of 18F- nifene with both kinetic modeling and graphical analysis tech- niques. Methods: Dynamic PET experiments were performed on 4 rhesus monkeys (female; age range, 9–13 y) using a small- animal PET scanner. Studies began with a high-specific-activity uch work in the last 15 y has been devoted toward 18 18 M F-nifene injection, followed by a coinjection of F-nifene and developing suitable PET radioligands to image a4b2* nico- unlabeled nifene at 60 min.
    [Show full text]
  • Micropet/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: a Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity
    International Scholarly Research Network ISRN Anesthesiology Volume 2012, Article ID 261640, 11 pages doi:10.5402/2012/261640 Research Article MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity Xuan Zhang,1 Merle G. Paule,1 Glenn D. Newport,1 Fang Liu,1 Ralph Callicott,1 Shuliang Liu,1 Marc S. Berridge,2, 3 Scott M. Apana,2, 3 William Slikker Jr.,1 and Cheng Wang1 1 National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA 2 3D Imaging, LLC, Little Rock, AR 72113, USA 3 University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Correspondence should be addressed to Cheng Wang, [email protected] Received 6 August 2012; Accepted 15 September 2012 Academic Editors: J. Abraini and J.-H. Baumert Copyright © 2012 Xuan Zhang 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. Background. The inhalation anesthetics nitrous oxide (N2O) and isoflurane (ISO) are used in surgical procedures for human infants. Injury to the central nervous system is often accompanied by localization of activated microglia or astrocytosis at the site of injury. The tracer that targets to the peripheral benzodiazepine receptor (PBR), [18F]N-2-(2-fluoroethoxy)benzyl)- N-(4-phenoxypyridin-3-yl)acetamide ([18F]-FEPPA), has been reported as a sensitive biomarker for the detection of neuronal damage/inflammation. Methods. On postnatal day (PND) 5 or 6 rhesus monkey neonates were exposed to a mixture of N2O/oxygen and ISO for 8 hours and control monkeys were exposed to room air.
    [Show full text]
  • In the Basilar Artery
    OPEN ACCESS International Journal of Pharmacology ISSN 1811-7775 DOI: 10.3923/ijp.2017.1.10 Review Article Involvement of Arachidonic Acid Metabolites Pathway and Nicotinic Acetylcholine Receptors (nAChRs) on Nicotine-induced Contractions (or Relaxations) in the Basilar Artery 1Yifan Li, 2Dan Luo, 2Xuejiao Chen, 2Jie Li, 1Liang Yan, 1Tong Li, 3Yingliang Zhao, 4Hui Liu, 2Xu Ji and 1Xiao Ma 1Key Laboratory of Pu-erh Tea Science of Ministry of Education, Yunnan Research Center for Advanced Tea Processing, Yunnan Agricultural University, No. 452 FengYuan Street, Kunming, 650201 Yunnan, China 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201 Yunnan, China 3Technology center of China Tobacco Yunnan Industry Co., Ltd, Kunming, Yunnan, China 4Urology, The Second Hospital of Dalian Medical University, Dalian, 116021 Liaoning, China Abstract Smoking is one of the most important risk factors for cerebral circulatory disorders and nicotine is considered to be the major pathogenic compound in cigarette smoke. Amelioration of nicotine-induced vasoconstrictions (or vasodilations) may provide a therapeutic target for the treatment of stroke. This study will review the involvement of arachidonic acid metabolites pathway and nicotinic acetylcholine receptors (nAChRs) on nicotine-induced contractions (or relaxations) in the basilar artery. Arachidonic acid metabolites pathway and nAChRs may be new drug targets and their selectivity antagonists (or agonists) may be new therapeutic drugs for the treatment of stroke. Key words: Basilar artery, nicotine, vasoconstriction, vasorelaxation, arachidinic acid, nicotinic acetylcholine receptors (nAChRs), endothelium Received: March 24, 2016 Accepted: October 19, 2016 Published: December 15, 2016 Citation: Yifan Li, Dan Luo, Xuejiao Chen, Jie Li, Liang Yan, Tong Li, Yingliang Zhao, Hui Liu, Xu Ji and Xiao Ma, 2017.
    [Show full text]
  • Nicotine, Auditory Sensory Memory, and Sustained Attention in a Human Ketamine Model of Schizophrenia: Moderating Influence of a Hallucinatory Trait
    ORIGINAL RESEARCH ARTICLE published: 28 September 2012 doi: 10.3389/fphar.2012.00172 Nicotine, auditory sensory memory, and sustained attention in a human ketamine model of schizophrenia: moderating influence of a hallucinatory trait Verner Knott 1,2,3,4,5*, Dhrasti Shah3, Anne Millar 2, Judy McIntosh1, Derek Fisher 6, Crystal Blais 4 and Vadim Ilivitsky 5 1 Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada 2 Neuroscience Program, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada 3 School of Psychology, University of Ottawa, Ottawa, ON, Canada 4 Institute of Cognitive Science, Carleton University, Ottawa, ON, Canada 5 Royal Ottawa Mental Health Centre, Ottawa, ON, Canada 6 Department of Psychology, Mount Saint Vincent University, Halifax, NS, Canada Edited by: Background:The procognitive actions of the nicotinic acetylcholine receptor (nAChR) ago- Valentina Echeverria Moran, Bay Pines nist nicotine are believed, in part, to motivate the excessive cigarette smoking in schizophre- VA Medical Center, USA nia, a disorder associated with deficits in multiple cognitive domains, including low-level Reviewed by: Boris B. Quednow, University auditory sensory processes and higher-order attention-dependent operations. Objectives: Hospital of Psychiatry, Switzerland As N-methyl-d-aspartate receptor (NMDAR) hypofunction has been shown to contribute to Jason B. Wu, Cedars-Sinai Medical these cognitive impairments, the primary aims of this healthy volunteer study were to: (a) to Center, USA shed light on the separate and interactive roles of nAChR and NMDAR systems in the mod- *Correspondence: ulation of auditory sensory memory (and sustained attention), as indexed by the auditory Verner Knott, Clinical Neuroelectrophysiology and Cognitive event-related brain potential – mismatch negativity (MMN), and (b) to examine how these Research Laboratory, Institute of effects are moderated by a predisposition to auditory hallucinations/delusions (HD).
    [Show full text]
  • Development of Novel Approach to Diagnostic Imaging of Lung Cancer with 18F-Nifene PET/CT Using A/J Mice Treated with NNK
    Journal of Cancer Research & Therapy NobleResearch Galitovskiy V et al., J Cancer Res Ther 2013, 1(4): 128-137 www.nobleresearch.org 0 http://dx.doi.org/10.14312/2052-4994.2013-2 Original Research Open Access Development of novel approach to diagnostic imaging of lung cancer with 18F-Nifene PET/CT using A/J mice treated with NNK Galitovskiy V1, Kuruvilla SA2, Sevriokov E2, Corches A2, Pan ML2, Kalantari-Dehaghi M1, Chernyavsky AI1, Mukherjee J2,3 and Grando SA1,3 1 2 3Department of Dermatology, University of California-Irvine, Irvine, CA 92697, USA Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA Cancer Center and Research Institute, University of California-Irvine, Irvine, CA 92697, USA Abstract oncology. In this study, we utilized the tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancerDevelopment in A/J miceof novel as anmethods animal of model early fordiagnosis development of lung ofcancer a new is imaging one of the technique major tasks for early of contemporary diagnosis of clinicallung cancer. and experimental Lung cancer NNK treatment, followed by PET/CT scans with 18F-Nifene that binds to ofcells lungs in A/J were mice also overexpress obtained ex nicotinic vivo. CT acetylcholine revealed the receptors. presence ofLongitudinal lung nodules CT inscans 8-month were carriedNNK-treated out over mice, a period while ofcontrol 8 months mice after had no tumors. Imaging of live animals prior to necropsy allowed correlation4-made of results nicotinic of tumor receptors load via with PET/CT high affinity.and histopathological PET/CT scans 18F-Nifene was seen in the lungs of NNK-treated mice, whereas lungs of control mice showed only minor uptake of 18 18F-Nifene binding in lung in vivo and ex vivo demonstrated a findings.
    [Show full text]
  • Heightened Nicotinic Regulation of Auditory Cortex During Adolescence
    The Journal of Neuroscience, October 5, 2011 • 31(40):14367–14377 • 14367 Development/Plasticity/Repair Heightened Nicotinic Regulation of Auditory Cortex during Adolescence Hideki D. Kawai,1,2* Ho-An Kang,1* and Raju Metherate1 1Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California 92697, and 2Department of Bioinformatics, Faculty of Engineering, Soka University, Hachiouji, Tokyo 192-8577, Japan Adolescent smoking is associated with auditory-cognitive deficits and structural alterations to auditory thalamocortical systems, sug- gesting that higher auditory function is vulnerable to nicotine exposure during adolescence. Although nicotinic acetylcholine receptors (nAChRs) regulate thalamocortical processing in adults, it is not known whether they regulate processing at earlier ages since their expression pattern changes throughout postnatal development. Here we investigate nicotinic regulation of tone-evoked current source density (CSD) profiles in mouse primary auditory cortex from just after hearing onset until adulthood. At the youngest ages, systemic nicotine did not affect CSD profiles. However, beginning in early adolescence nicotine enhanced characteristic frequency (CF)-evoked responses in layers 2–4 by enhancing thalamocortical, early intracortical, and late intracortical response components. Nicotinic respon- siveness developed rapidly and peaked over the course of adolescence, then declined thereafter. Generally, responsiveness in females developed more quickly, peaked earlier, and declined more abruptly and fully than in males. In contrast to the enhancement of CF-evoked responses, nicotine suppressed shorter-latency intracortical responses to spectrally distant (non-CF) stimuli while enhancing longer- latency responses. Intracortical infusion of nAChR antagonists showed that enhancement of CF-evoked intracortical processing involves ␣4␤2*, but not ␣7, nAChRs, whereas both receptor subtypes regulate non-CF-evoked late intracortical responses.
    [Show full text]
  • 18F-Niofene) As a Potential Imaging Agent for Nicotinic Α4β2 Receptors
    Am J Nucl Med Mol Imaging 2014;4(4):354-364 www.ajnmmi.us /ISSN:2160-8407/ajnmmi0000467 Original Article Synthesis and evaluation of 2-18F-fluoro-5-iodo-3- [2-(S)-3,4-dehydropyrrolinylmethoxy]pyridine (18F-Niofene) as a potential imaging agent for nicotinic α4β2 receptors Sharon A Kuruvilla1, Ansel T Hillmer2, Dustin W Wooten2, Ashna Patel1, Bradley T Christian2, Jogeshwar Mukherjee1 1Preclinical Imaging, Department of Radiological Sciences, University of California, Irvine, CA 92697, USA; 2De- partment of Medical Physics, University of Wisconsin, Madison, WI 53705, USA Received April 8, 2014; Accepted April 22, 2014; Epub June 7, 2014; Published June 15, 2014 Abstract: Nicotinic α4β2 acetylcholine receptors (nAChRs) have been implicated in various pathophysiologies in- cluding neurodegenerative diseases. Currently, 2-18F-A85380 (2-FA) and 5-123I-A85380 (5-IA) are used separately in human PET and SPECT studies respectively and require >4-6 hours of scanning. We have developed 2-fluoro-5-iodo- 3-[2-(S)-3-dehydropyrrolinylmethoxy]pyridine (niofene) as a potential PET/SPECT imaging agent for nAChRs with an aim to have rapid binding kinetics similar to that of 18F-nifene used in PET studies. Niofene exhibited a 10-fold better in vitro binding affinity in rat brain than that of nicotine. The relative binding of niofene was similar to that of niodene and twice as better as that of nifene. In vitro autoradiography in rat brain slices alongside niodene indicated selec- tive binding of niofene to regions consistent with α4β2 receptor distribution. Niofene, 10 nM, displaced >70% of 3H-cytisine bound to α4β2 receptors in rat brain slices.
    [Show full text]