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 β-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 β-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.
Bibliographical noteFunding Information:
The authors thank the Autism Research Foundation and its affiliated brain banks (Harvard Brain Bank, Universities of Maryland and Miami Brain Banks, in contract to NICHD) and the families of patients whose brains were donated for the generous gift of brain samples. We acknowledge the generous support of NARSAD and Stanley Foundations (SHF), Kunin Fund of St. Paul Foundation (SHF and GMR), and Stanley Scholar program (SCS). We are grateful to Ms. Susanne Lee for her statistical help and guidance. The secretarial assistance of Ms. Mary Rohe and Janet Holland is greatly appreciated.
- Gamma amino butyric acid
- Glutamic acid decarboxylase
- Parietal cortex
- Western blotting