天冬氨酸酰基转移酶缺乏症影响少突胶质细胞和髓鞘形成的早期产后发育。
Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination.
机构信息
Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Neurobiol Dis. 2010 Nov;40(2):432-43. doi: 10.1016/j.nbd.2010.07.003. Epub 2010 Jul 14.
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.
摘要
Canavan 病（CD）是一种神经退行性疾病，由天冬氨酸酰基转移酶（ASPA）缺乏引起。这种酶已经定位于少突胶质细胞；然而，ASPA 缺乏如何影响少突胶质细胞的发育仍不清楚。在正常小鼠中，ASPA 的表达模式与少突胶质细胞的成熟相吻合。因此，在 ASPA 缺乏的小鼠（CD 小鼠）中分析了出生后的少突胶质细胞成熟。在发育早期，CD 小鼠大脑中神经细胞标志物的表达减少，后来得到了代偿。此外，与野生型（WT）相比，CD 小鼠中的髓鞘蛋白水平降低，并且髓鞘异常。这些缺陷与乙酰化组蛋白 H3 的整体水平升高、染色质紧缩减少和 GFAP 蛋白（星形胶质细胞的标志物）增加有关。综上所述，这些发现强烈表明，在出生后的早期阶段，ASPA 缺乏会影响少突胶质细胞的成熟和髓鞘形成。
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