GABA(A) receptor downregulation in brains of subjects with autism.
Gamma-aminobutyric acid A (GABA(A)) receptors are ligand-gated ion channels responsible for mediation of fast inhibitory action of GABA in the brain. Preliminary reports have demonstrated altered expression of GABA receptors in the brains of subjects with autism suggesting GABA/glutamate system dysregulation. We investigated the expression of four GABA(A) receptor subunits and observed significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex (Brodmann's Area 40 (BA40)), while GABRA1 and GABRB3 were significantly altered in cerebellum, and GABRA1 was significantly altered in superior frontal cortex (BA9). The presence of seizure disorder did not have a significant impact on GABA(A) receptor subunit expression in the three brain areas. Our results demonstrate that GABA(A) receptors are reduced in three brain regions that have previously been implicated in the pathogenesis of autism, suggesting widespread GABAergic dysfunction in the brains of subjects with autism.
Fatemi
S Hossein
SH
Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA. fatem002@umn.edu
Reutiman
Teri J
TJ
Folsom
Timothy D
TD
Thuras
Paul D
PD
D000328:Adult; D001321:Autistic Disorder / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004827:Epilepsy / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000378:metabolism; D011180:Postmortem Changes; D011963:Receptors, GABA-A / Q000378:metabolism*; D055815:Young Adult
C546240:GABRA1 protein, human; C484841:GABRA2 protein, human; C546257:GABRA3 protein, human; C546273:GABRB3 protein, human; D011963:Receptors, GABA-A