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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...

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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
Descripción
Sumario: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.