GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models

Copyright © 2018 The Authors, some rights reserved. Preliminary studies have suggested that -aminobutyric acid type A (GABAA) receptors, and potentially the GABAA 5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, an...

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Main Authors: Horder, J., Andersson, M., Mendez, M., Singh, N., Tangen, A., Lundberg, J., Gee, A., Halldin, C., Veronese, M., Bolte, Sven, Farde, L., Sementa, T., Cash, D., Higgins, K., Spain, D., Turkheimer, F., Mick, I., Selvaraj, S., Nutt, D., Lingford-Hughes, A., Howes, O., Murphy, D., Borg, J.
Format: Journal Article
Published: 2018
Online Access:http://hdl.handle.net/20.500.11937/72449
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author Horder, J.
Andersson, M.
Mendez, M.
Singh, N.
Tangen, A.
Lundberg, J.
Gee, A.
Halldin, C.
Veronese, M.
Bolte, Sven
Farde, L.
Sementa, T.
Cash, D.
Higgins, K.
Spain, D.
Turkheimer, F.
Mick, I.
Selvaraj, S.
Nutt, D.
Lingford-Hughes, A.
Howes, O.
Murphy, D.
Borg, J.
author_facet Horder, J.
Andersson, M.
Mendez, M.
Singh, N.
Tangen, A.
Lundberg, J.
Gee, A.
Halldin, C.
Veronese, M.
Bolte, Sven
Farde, L.
Sementa, T.
Cash, D.
Higgins, K.
Spain, D.
Turkheimer, F.
Mick, I.
Selvaraj, S.
Nutt, D.
Lingford-Hughes, A.
Howes, O.
Murphy, D.
Borg, J.
author_sort Horder, J.
building Curtin Institutional Repository
collection Online Access
description Copyright © 2018 The Authors, some rights reserved. Preliminary studies have suggested that -aminobutyric acid type A (GABAA) receptors, and potentially the GABAA 5 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 5 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 5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA 5 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.
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spelling curtin-20.500.11937-724492019-03-22T02:45:22Z GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models Horder, J. Andersson, M. Mendez, M. Singh, N. Tangen, A. Lundberg, J. Gee, A. Halldin, C. Veronese, M. Bolte, Sven Farde, L. Sementa, T. Cash, D. Higgins, K. Spain, D. Turkheimer, F. Mick, I. Selvaraj, S. Nutt, D. Lingford-Hughes, A. Howes, O. Murphy, D. Borg, J. Copyright © 2018 The Authors, some rights reserved. Preliminary studies have suggested that -aminobutyric acid type A (GABAA) receptors, and potentially the GABAA 5 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 5 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 5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA 5 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/72449 10.1126/scitranslmed.aam8434 restricted
spellingShingle Horder, J.
Andersson, M.
Mendez, M.
Singh, N.
Tangen, A.
Lundberg, J.
Gee, A.
Halldin, C.
Veronese, M.
Bolte, Sven
Farde, L.
Sementa, T.
Cash, D.
Higgins, K.
Spain, D.
Turkheimer, F.
Mick, I.
Selvaraj, S.
Nutt, D.
Lingford-Hughes, A.
Howes, O.
Murphy, D.
Borg, J.
GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models
title GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models
title_full GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models
title_fullStr GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models
title_full_unstemmed GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models
title_short GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models
title_sort gabaa receptor availability is not altered in adults with autism spectrum disorder or in mouse models
url http://hdl.handle.net/20.500.11937/72449