TY - JOUR
T1 - Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABAAR subunits
AU - Sequeira, Adolfo
AU - Shen, Kevin
AU - Gottlieb, Assaf
AU - Limon, Agenor
N1 - Funding Information:
The authors thank Dr. N. C. Spitzer, Dr. M. P. Vawter, and Dr. B. E. Hjelm for their insightful discussions of the manuscript. This work was supported by NIH research grants R01MH097082 (to A.S.), R21MH113177 (to A.L.), and R21AG053740 (to A.L.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Altered expression of GABA receptors (GABAARs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABAAR 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 GABAAR 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 GABAR 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 GABAAR subunits after physiological, pharmacological or pathological challenges.
AB - Altered expression of GABA receptors (GABAARs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABAAR 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 GABAAR 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 GABAR 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 GABAAR subunits after physiological, pharmacological or pathological challenges.
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U2 - 10.1038/s42003-019-0413-7
DO - 10.1038/s42003-019-0413-7
M3 - Article
C2 - 31069263
AN - SCOPUS:85071161538
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 153
ER -