Cargando…

Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits

Altered expression of GABA receptors (GABA(A)Rs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABA(A)R subunit expression in healthy human brains, heteromeric assembly of major isoforms, and their collective organization across healthy...

Descripción completa

Detalles Bibliográficos
Autores principales: Sequeira, Adolfo, Shen, Kevin, Gottlieb, Assaf, Limon, Agenor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494906/
https://www.ncbi.nlm.nih.gov/pubmed/31069263
http://dx.doi.org/10.1038/s42003-019-0413-7
_version_ 1783415298338062336
author Sequeira, Adolfo
Shen, Kevin
Gottlieb, Assaf
Limon, Agenor
author_facet Sequeira, Adolfo
Shen, Kevin
Gottlieb, Assaf
Limon, Agenor
author_sort Sequeira, Adolfo
collection PubMed
description Altered expression of GABA receptors (GABA(A)Rs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABA(A)R subunit expression in healthy human brains, heteromeric assembly of major isoforms, and their collective organization across healthy individuals, are major roadblocks to understanding their role in non-physiological states. Here, by using microarray and RNA-Seq datasets—from single cell nuclei to global brain expression—from the Allen Institute, we find that transcriptional expression of GABA(A)R subunits is anatomically organized according to their neurodevelopmental origin. The data show a combination of complementary and mutually-exclusive expression patterns that delineate major isoforms, and which is highly stereotypical across brains from control donors. We summarize the region-specific signature of GAB(A)R subunits per subject and its variability in a control population sample that can be used as a reference for remodeling changes during homeostatic rearrangements of GABA(A)R subunits after physiological, pharmacological or pathological challenges.
format Online
Article
Text
id pubmed-6494906
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64949062019-05-08 Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits Sequeira, Adolfo Shen, Kevin Gottlieb, Assaf Limon, Agenor Commun Biol Article Altered expression of GABA receptors (GABA(A)Rs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABA(A)R subunit expression in healthy human brains, heteromeric assembly of major isoforms, and their collective organization across healthy individuals, are major roadblocks to understanding their role in non-physiological states. Here, by using microarray and RNA-Seq datasets—from single cell nuclei to global brain expression—from the Allen Institute, we find that transcriptional expression of GABA(A)R subunits is anatomically organized according to their neurodevelopmental origin. The data show a combination of complementary and mutually-exclusive expression patterns that delineate major isoforms, and which is highly stereotypical across brains from control donors. We summarize the region-specific signature of GAB(A)R subunits per subject and its variability in a control population sample that can be used as a reference for remodeling changes during homeostatic rearrangements of GABA(A)R subunits after physiological, pharmacological or pathological challenges. Nature Publishing Group UK 2019-05-01 /pmc/articles/PMC6494906/ /pubmed/31069263 http://dx.doi.org/10.1038/s42003-019-0413-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sequeira, Adolfo
Shen, Kevin
Gottlieb, Assaf
Limon, Agenor
Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits
title Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits
title_full Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits
title_fullStr Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits
title_full_unstemmed Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits
title_short Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABA(A)R subunits
title_sort human brain transcriptome analysis finds region- and subject-specific expression signatures of gaba(a)r subunits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494906/
https://www.ncbi.nlm.nih.gov/pubmed/31069263
http://dx.doi.org/10.1038/s42003-019-0413-7
work_keys_str_mv AT sequeiraadolfo humanbraintranscriptomeanalysisfindsregionandsubjectspecificexpressionsignaturesofgabaarsubunits
AT shenkevin humanbraintranscriptomeanalysisfindsregionandsubjectspecificexpressionsignaturesofgabaarsubunits
AT gottliebassaf humanbraintranscriptomeanalysisfindsregionandsubjectspecificexpressionsignaturesofgabaarsubunits
AT limonagenor humanbraintranscriptomeanalysisfindsregionandsubjectspecificexpressionsignaturesofgabaarsubunits