Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination

Natalia S. Mattan, Cristina A. Ghiani, Marcia Lloyd, Reuben Matalon, Dean Bok, Patrizia Casaccia, Jean de Vellis

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Canavan disease (CD) is a neurodegenerative disease, caused by a deficiency in the enzyme aspartoacylase (ASPA). This enzyme has been localized to oligodendrocytes; however, it is still undefined how ASPA deficiency affects oligodendrocyte development. In normal mice the pattern of ASPA expression coincides with oligodendrocyte maturation. Therefore, postnatal oligodendrocyte maturation was analyzed in ASPA-deficient mice (CD mice). Early in development, CD mice brains showed decreased expression of neural cell markers that was later compensated. In addition, the levels of myelin proteins were decreased along with abnormal myelination in CD mice compared to wild-type (WT). These defects were associated with increased global levels of acetylated histone H3, decreased chromatin compaction and increased GFAP protein, a marker for astrogliosis. Together, these findings strongly suggest that, early in postnatal development, ASPA deficiency affects oligodendrocyte maturation and myelination.

Original languageEnglish (US)
Pages (from-to)432-443
Number of pages12
JournalNeurobiology of Disease
Volume40
Issue number2
DOIs
StatePublished - Nov 2010

Keywords

  • Aspartoacylase
  • Canavan disease
  • Development
  • Leukodystrophy
  • Neural cells
  • Oligodendrocytes

ASJC Scopus subject areas

  • Neurology

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