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A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mech...

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Autores principales: Nørgaard, Martin, Beliveau, Vincent, Ganz, Melanie, Svarer, Claus, Pinborg, Lars H, Keller, Sune H, Jensen, Peter S, Greve, Douglas N., Knudsen, Gitte M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256681/
https://www.ncbi.nlm.nih.gov/pubmed/33610745
http://dx.doi.org/10.1016/j.neuroimage.2021.117878
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author Nørgaard, Martin
Beliveau, Vincent
Ganz, Melanie
Svarer, Claus
Pinborg, Lars H
Keller, Sune H
Jensen, Peter S
Greve, Douglas N.
Knudsen, Gitte M.
author_facet Nørgaard, Martin
Beliveau, Vincent
Ganz, Melanie
Svarer, Claus
Pinborg, Lars H
Keller, Sune H
Jensen, Peter S
Greve, Douglas N.
Knudsen, Gitte M.
author_sort Nørgaard, Martin
collection PubMed
description Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system. Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABA(A) receptors (GABA(A) Rs), generated on the basis of in vivo [(11)C]flumazenil Positron Emission Tomography (PET) data. Next, based on ex vivo autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association between BZR protein density and ex vivo mRNA expression for the 19 subunits in the GABA(A) R, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABA(A) R and the BZR density at each location in the brain.
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spelling pubmed-82566812021-07-05 A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors Nørgaard, Martin Beliveau, Vincent Ganz, Melanie Svarer, Claus Pinborg, Lars H Keller, Sune H Jensen, Peter S Greve, Douglas N. Knudsen, Gitte M. Neuroimage Article Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system. Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABA(A) receptors (GABA(A) Rs), generated on the basis of in vivo [(11)C]flumazenil Positron Emission Tomography (PET) data. Next, based on ex vivo autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association between BZR protein density and ex vivo mRNA expression for the 19 subunits in the GABA(A) R, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABA(A) R and the BZR density at each location in the brain. 2021-02-18 2021-05-15 /pmc/articles/PMC8256681/ /pubmed/33610745 http://dx.doi.org/10.1016/j.neuroimage.2021.117878 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Article
Nørgaard, Martin
Beliveau, Vincent
Ganz, Melanie
Svarer, Claus
Pinborg, Lars H
Keller, Sune H
Jensen, Peter S
Greve, Douglas N.
Knudsen, Gitte M.
A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors
title A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors
title_full A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors
title_fullStr A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors
title_full_unstemmed A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors
title_short A high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of GABA(A) receptors
title_sort high-resolution in vivo atlas of the human brain’s benzodiazepine binding site of gaba(a) receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256681/
https://www.ncbi.nlm.nih.gov/pubmed/33610745
http://dx.doi.org/10.1016/j.neuroimage.2021.117878
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