Postmortem brain abnormalities of the glutamate neurotransmitter system in autism

A. E. Purcell, O. H. Jeon, A. W. Zimmerman, Mary E Blue, Jonathan A. Pevsner

Research output: Contribution to journalArticle

Abstract

Background: Studies examining the brains of individuals with autism have identified anatomic and pathologic changes in regions such as the cerebellum and hippocampus. Little, if anything, is known, however, about the molecules that are involved in the pathogenesis of this disorder. Objective: To identify genes with abnormal expression levels in the cerebella of subjects with autism. Methods: Brain samples from a total of 10 individuals with autism and 23 matched controls were collected, mainly from the cerebellum. Two cDNA microarray technologies were used to identify genes that were significantly up- or downregulated in autism. The abnormal mRNA or protein levels of several genes identified by microarray analysis were investigated using PCR with reverse transcription and Western blotting, α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)- and NMDA-type glutamate receptor densities were examined with receptor autoradiography in the cerebellum, caudate-putamen, and prefrontal cortex. Results: The mRNA levels of several genes were significantly increased in autism, including excitatory amino acid transporter 1 and glutamate receptor AMPA 1, two members of the glutamate system. Abnormalities in the protein or mRNA levels of several additional molecules in the glutamate system were identified on further analysis, including glutamate receptor binding proteins. AMPA-type glutamate receptor density was decreased in the cerebellum of individuals with autism (p <0.05). Conclusions: Subjects with autism may have specific abnormalities in the AMPA-type glutamate receptors and glutamate transporters in the cerebellum. These abnormalities may be directly involved in the pathogenesis of the disorder.

Original languageEnglish (US)
Pages (from-to)1618-1628
Number of pages11
JournalNeurology
Volume57
Issue number9
StatePublished - Nov 13 2001

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Autistic Disorder
Neurotransmitter Agents
Glutamic Acid
Cerebellum
Glutamate Receptors
Brain
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Messenger RNA
Genes
Excitatory Amino Acid Transporter 1
Amino Acid Transport System X-AG
Putamen
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Autoradiography
Reverse Transcription
Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)

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Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. / Purcell, A. E.; Jeon, O. H.; Zimmerman, A. W.; Blue, Mary E; Pevsner, Jonathan A.

In: Neurology, Vol. 57, No. 9, 13.11.2001, p. 1618-1628.

Research output: Contribution to journalArticle

Purcell, AE, Jeon, OH, Zimmerman, AW, Blue, ME & Pevsner, JA 2001, 'Postmortem brain abnormalities of the glutamate neurotransmitter system in autism', Neurology, vol. 57, no. 9, pp. 1618-1628.
Purcell, A. E. ; Jeon, O. H. ; Zimmerman, A. W. ; Blue, Mary E ; Pevsner, Jonathan A. / Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. In: Neurology. 2001 ; Vol. 57, No. 9. pp. 1618-1628.
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