Expression of glutamate transporter, GABRA6, serine proteinase inhibitor 2 and low levels of glutamate and GABA in the brain of knock-out mouse for Canavan disease

Sankar Surendran, Peter L. Rady, Kimberlee Michals-Matalon, Michael J. Quast, David K. Rassin, Gerald A. Campbell, Ed L. Ezell, Jingna Wei, Stephen K. Tyring, Sylvia Szucs, Reuben Matalon

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Canavan disease (CD) is an autosomal recessive leukodystrophy characterized by spongy degeneration of the brain. The clinical features of CD are hypotonia, megalencephaly, and mental retardation leading to early death. While aspartoacylase (ASPA) activity increases with age in the wild type mouse brain, there is no ASPA activity in the CD mouse brain. So far ASPA deficiency and elevated NAA have been ascribed with the CD. Other factors affecting the brain that result from ASPA deficiency may lead pathophysiology of CD. The NMR spectra and amino acid analysis showed lower levels of glutamate and γ-aminobutyric acid in the CD mouse brain compared to the wild type. Microarray gene expression on CD mouse brain showed glutamate transporter-EAAT4 and γ-aminobutyric acid-A receptor, subunit α6 (GABRA6) were lower 9.7- and 119.1-fold, respectively. Serine proteinase inhibitor 2 (Spi2) was 29.9-fold higher in the CD mouse brain compared to the wild type. The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR. This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD.

Original languageEnglish (US)
Pages (from-to)427-435
Number of pages9
JournalBrain Research Bulletin
Volume61
Issue number4
DOIs
StatePublished - Aug 30 2003

Keywords

  • Canavan disease
  • EAAT4
  • GABA
  • GABRA6
  • Glutamate
  • Spi2

ASJC Scopus subject areas

  • Neuroscience(all)

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