Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination.
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.
Mattan
Natalia S
NS
Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Ghiani
Cristina A
CA
Lloyd
Marcia
M
Matalon
Reuben
R
Bok
Dean
D
Casaccia
Patrizia
P
de Vellis
Jean
J
D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017825:Canavan Disease / Q000378:metabolism* / Q000473:pathology*; D002843:Chromatin / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D015415:Biomarkers; D002843:Chromatin; D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D000581:Amidohydrolases; C019751:aspartoacylase