Cited by 500Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices

Fatemi, S.Hossein, Halt, Amy R, Stary, Joel M, Kanodia, Reena, Schulz, S.Charles, Realmuto, George R·2002·Biological Psychiatry

Abstract

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.

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Crossref · 10.1016/s0006-3223(02)01430-0

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Authors
Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., & Realmuto, G. R.
Affiliations
University of Minnesota (US)
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2002-10
Volume
52
Issue
8
Pages
805-810
ISSN
0006-3223 (ISSN-L)
OpenAlex
W2047266773
Cited by
500
References
38
Citations by year
2026: 10 · 2025: 16 · 2024: 11 · 2023: 24 · 2022: 27 · 2021: 16 · 2020: 19 · 2019: 19 · 2018: 26 · 2017: 20 · 2016: 31 · 2015: 25 · 2014: 44 · 2013: 34 · 2012: 30
FWCI
5.34
Type
journal article
Language
en
Open access
closed
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
glutamic acid decarboxylase, GAD65, GAD67, autism spectrum disorder, parietal cortex, cerebellum, glutamate, GABA, postmortem brain, enzyme deficiency
MeSH terms
Adult, Autistic Disorder, Cerebellar Cortex, Female, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Humans, Male, Molecular Weight, Parietal Lobe, Blotting, Western

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