@article{d9b6065cd8094a9590aa525f0da30e16,
title = "Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination",
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.",
keywords = "Aspartoacylase, Canavan disease, Development, Leukodystrophy, Neural cells, Oligodendrocytes",
author = "Mattan, {Natalia S.} and Ghiani, {Cristina A.} and Marcia Lloyd and Reuben Matalon and Dean Bok and Patrizia Casaccia and {de Vellis}, Jean",
note = "Funding Information: The authors are grateful to Dr. Carolyn Houser and Birgitta Sjostrand for help and advices with electron microscopy, and to Scott Fish, Teresita Yang and Jemily Malvar for technical assistance. The authors also wish to thank Dr. Esteban Dell'Angelica for insightful advice and help with fluorescent microscopy, Dr. Ellen Carpenter, Elvira Khialeeva, and Diana Anthony for their help with the H&E staining technique, Drs. Anthony Campagnoni and Pablo Paez for help with the use of the Olympus Spinning Disc Confocal Inverted Microscope. We would also like to thank Donna Crandall of the UCLA-IDDRC Media Core for help with the figures. This work was supported by grants from the NINDS-Rita L. Kirschstein NRSA Fellowship to N.S.M., a Stein-Oppenheimer Endowment Award to C.A.G. and J.d.V., NIH grants P01-HD06576 , HD04612 and NMSS PP1585 to J.d.V., RO1-NS42925-08 and ARRA supplement NS42925-S1 to P.C. and the Jules Stein Core grant at UCLA-EY00331 to D.B. ",
year = "2010",
month = nov,
doi = "10.1016/j.nbd.2010.07.003",
language = "English (US)",
volume = "40",
pages = "432--443",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "2",
}