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

• Published in: Communications biology Vol. 2; p. 153
• Main Authors: Sequeira, Adolfo, Shen, Kevin, Gottlieb, Assaf, Limon, Agenor
• Format: Journal Article
• Language: English
• Published: England 01.05.2019
• Subjects: Adult; Amygdala - anatomy & histology; Amygdala - metabolism; Brain - anatomy & histology; Brain - metabolism; Cerebral Cortex - anatomy & histology; Cerebral Cortex - metabolism; Corpus Striatum - anatomy & histology; Corpus Striatum - metabolism; Datasets as Topic; Female; Gene Expression Profiling; Hippocampus - anatomy & histology; Hippocampus - metabolism; Humans; Hypothalamus - anatomy & histology; Hypothalamus - metabolism; Male; Mesencephalon - anatomy & histology; Mesencephalon - metabolism; Middle Aged; Organ Specificity; Phylogeny; Protein Subunits - classification; Protein Subunits - genetics; Protein Subunits - metabolism; Receptors, GABA-A - classification; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Transcriptome; Microarrays; Ion channels in the nervous system
• ISSN: 2399-3642
• DOI: 10.1038/s42003-019-0413-7

Altered expression of GABA receptors (GABA Rs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABA 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 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 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 R subunits after physiological, pharmacological or pathological challenges.