GABA(A) receptor availability is not altered in adults with autism spectrum disorder or in mouse models

File Description SizeFormat 
aam8434_ArticleContent_v4.docxAccepted version1.03 MBMicrosoft WordView/Open
8c6b386e-66fb-4b23-92a5-d697c13fe32d.htmAccepted version41.21 kBHTMLView/Open
aam8434_Figure_fig1_seq4_v1.tifAccepted version8.03 MBTIFFView/Open
aam8434_Figure_fig2_seq1_v1.aiAccepted version1.09 MBPostscriptView/Open
aam8434_Figure_fig3_seq5_v1.tifAccepted version451.9 kBTIFFView/Open
aam8434_Figure_fig4_seq2_v1.aiAccepted version1.09 MBPostscriptView/Open
aam8434_Figure_fig5_seq3_v1.aiAccepted version1.49 MBPostscriptView/Open
aam8434_SupplementalMaterial_v4.docxAccepted version939.56 kBMicrosoft WordView/Open
Title: GABA(A) receptor availability is not altered in adults with autism spectrum disorder or in mouse models
Authors: Horder, J
Andersson, M
Mendez, MA
Singh, N
Tangen, A
Lundberg, J
Gee, A
Halldin, C
Veronese, M
Bolte, S
Farde, L
Sementa, T
Cash, D
Higgins, K
Spain, D
Turkheimer, F
Mick, I
Selvaraj, S
Nutt, DJ
Lingford-Hughes, A
Howes, OD
Murphy, DG
Borg, J
Item Type: Journal Article
Abstract: Preliminary studies have suggested that γ-aminobutyric acid type A (GABAA) receptors, and potentially the GABAA α5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, and these studies did not compare findings across different species. We measured both total GABAA and GABAA α5 receptor availability in two positron emission tomography imaging studies. We used the tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control individuals without ASD. All participants were free of medications. We also performed autoradiography, using the same tracers, in three mouse models of ASD: the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a 16p11.2 deletion. We found no differences in GABAA receptor or GABAA α5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA α5 subunit availability in any of the three mouse models. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task. Our data suggest that GABAA receptor availability may be normal in adults with ASD, although GABA signaling may be functionally impaired.
Issue Date: 3-Oct-2018
Date of Acceptance: 15-Dec-2017
URI: http://hdl.handle.net/10044/1/64171
DOI: https://dx.doi.org/10.1126/scitranslmed.aam8434
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science
Journal / Book Title: Science Translational Medicine
Volume: 10
Issue: 461
Copyright Statement: © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuse
Sponsor/Funder: Medical Research Council (MRC)
Commission of the European Communities
Funder's Grant Number: G1002226
607616
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
POSITRON-EMISSION-TOMOGRAPHY
HUMAN CEREBRAL-CORTEX
BENZODIAZEPINE-RECEPTOR
ASPERGER-SYNDROME
MOTION PERCEPTION
IN-VIVO
PET
BINDING
SYSTEM
BRAIN
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
POSITRON-EMISSION-TOMOGRAPHY
HUMAN CEREBRAL-CORTEX
BENZODIAZEPINE-RECEPTOR
ASPERGER-SYNDROME
MOTION PERCEPTION
IN-VIVO
PET
BINDING
SYSTEM
BRAIN
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Article Number: ARTN eaam8434
Appears in Collections:Clinical Sciences
Imaging Sciences
Department of Medicine
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx