Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices
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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GAD 65 and 67 proteins are reduced in the cerebella of subjects with autism.
“It has been shown that GAD 65 and 67 proteins are reduced in the cerebella of subjects with autism [122, 125].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [122]
ASD is associated with altered expression of various GABA-receptor subtypes.
“altered expression of various GABA-receptor subtypes (Fatemi et al., 2002”
From Neuronal Dynamics and Neuropsychiatric Disorders: Toward a Translational Paradigm for Dysfunctional Large-Scale Networks (2012) · cites this paper as Fatemi et al., 2002
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Bent, S., & Hendren, R. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.011 · Cited by 25 · see citing works
Hannant, P., Cassidy, S., Renshaw, D., & Joyce, A. (2021) · Nutritional Neuroscience · doi:10.1080/1028415x.2019.1588486 · Cited by 16 · see citing works
GABA-mediated inhibition in visual feedback neurons fine-tunes <i>Drosophila</i> male courtship
Mabuchi, Y., Cui, X., Xie, L., Kim, H., Jiang, T., & Yapici, N. (2023) · doi:10.1101/2023.01.25.525544 · Cited by 1 · see citing works
- Authors
- Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., & Realmuto, G. R.
- Affiliations
- University of Minnesota (US)
- ORCID
- Fatemi, S.Hossein
- 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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