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

Neurobiology of Disease (Nov 2010)

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

Affiliations

Natalia S. Mattan: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Cristina A. Ghiani: Department of Psychiatry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Marcia Lloyd: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Reuben Matalon: Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555, USA
Dean Bok: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Patrizia Casaccia: Departments of Neuroscience and Genetics and Genomics, Mount Sinai School of Medicine, New York, NY 10029, USA
Jean de Vellis: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Corresponding author. UCLA-Intellectual and Developmental Disabilities Research Center, 635 Charles E Young Drive South, Los Angeles, CA 90095-7332, USA. Fax: +1 310 206 5061.

Journal volume & issue: Vol. 40, no. 2
pp. 432 – 443

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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