Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices.
BACKGROUND
A limited number of reports have demonstrated abnormalities involving the glutamate and gamma amino butyric acid systems in blood and platelets of subjects with autism. To further investigate these studies, brain levels of rate limiting enzyme, glutamic acid decarboxylase, which is responsible for normal conversion of glutamate to gamma amino butyric acid in the brain, were investigated.


METHODS
Postmortem cerebellar and parietal cortices of age (mean +/- SD for controls 23 +/- 4.2, autistic 25.2 +/- 5.2 cerebellum; controls 23.5 +/- 4.8, autistic 21.6 +/- 3.8 parietal cortex), gender and postmortem interval-matched autistic and control subjects (n = 8 control, n = 5 autism, cerebellum; n = 4 control, n = 5 autism, parietal cortex) were subjected to SDS-PAGE and western blotting. Brain levels of glutamic acid decarboxylase proteins of 65 and 67 kDa and beta-actin were determined.


RESULTS
Glutamic acid decarboxylase protein of 65 kDa was reduced by 48% and 50% in parietal and cerebellar (p <.02) areas of autistic brains versus controls respectively. By the same token, glutamic acid decarboxylase protein of 67 kDa was reduced by 61% and 51% in parietal (p <.03) and cerebellar areas of autistic brains versus controls respectively. Brain levels of beta-actin were essentially similar in both groups.


CONCLUSIONS
The observed reductions in glutamic acid decarboxylase 65 and 67 kDa levels may account for reported increases of glutamate in blood and platelets of autistic subjects. Glutamic acid decarboxylase deficiency may be due to or associated with abnormalities in levels of glutamate/gamma amino butyric acid, or transporter/receptor density in autistic brain.
Fatemi
S Hossein
SH
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware Street SE, Mayo Building, Box 392, Minneapolis, MN 55455, USA.
Halt
Amy R
AR
Stary
Joel M
JM
Kanodia
Reena
R
Schulz
S Charles
SC
Realmuto
George R
GR
D000328:Adult; D001321:Autistic Disorder / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002525:Cerebellar Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D008297:Male; D008970:Molecular Weight; D010296:Parietal Lobe / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase