Lysosomal sulfatide storage in the brain of arylsulfatase A-deficient mice: cellular alterations and topographic distribution
Lysosomal sulfatide storage in the brain of arylsulfatase A-deficient mice: cellular alterations and topographic distribution
复制标题
芳基硫酸酯酶 A 缺陷小鼠大脑中溶酶体硫苷脂的储存：细胞改变和地形分布
作者：
D. Wittke;D. Hartmann;V. Gieselmann;R. Lüllmann
溶酶体酶芳基硫酸酯酶A(AsA)的遗传缺陷导致硫脂的溶酶体储存，并导致人类中枢神经系统显著的脱髓鞘(异色性脑白质营养不良，MLD)。作为一种动物模型，ASA-/-小鼠以前是通过破坏ASA基因而产生的，并已知具有与人类MLD相似的溶酶体硫脂储存，此外，由于听觉通路初级神经元的退化而变聋。本研究研究了几天至24个月龄的ASA-/-小鼠中枢神经系统内硫脂储存的细胞和局部分布。超微结构和阿尔新蓝组织化学染色检测到硫脂积聚。幼年小鼠的少突胶质细胞和神经元中存在硫脂储存，成年小鼠的小胶质细胞(吞噬细胞)中存在硫脂储存。神经元硫脂的储存主要集中在延髓和脑桥的许多核，以及中脑和前脑的几个核。老年AsA-/-小鼠白质束中储存硫脂的吞噬细胞最为常见，但未见广泛的脱髓鞘现象。老年AsA-/-小鼠听觉通路的两个核团(耳蜗腹核核和斜方体核)有神经元丢失。硫脂储存在ASA-/-小鼠中枢神经系统中的分布模式与报道的人类MLD数据基本一致。然而，一个目前仍未解释的重要区别是，直到2岁的ASA-/-小鼠的中枢神经系统没有明显的脱髓鞘。
Inherited deficiency for the lysosomal enzyme arylsulfatase A (ASA) leads to lysosomal storage of sulfatides and to dramatic demyelination in the CNS of humans (metachromatic leukodystrophy, MLD). As an animal model, ASA–/– mice have previously been generated by disruption of the ASA gene and are known to develop lysosomal sulfatide storage similar to that in human MLD, and, moreover, to become deaf because of degeneration of the primary neurons of the auditory pathway. The present study deals with the cellular and topographic distribution of sulfatide storage throughout the CNS of ASA–/– mice between a few days and 24 months of age. Sulfatide accumulation was detected on the ultrastructural level and by histochemical staining with alcian blue. Sulfatide storage was found in oligodendroglia and neurons in young mice, and in activated microglia (phagocytes) in adult mice. Neuronal sulfatide storage was most prominent in many nuclei of the medulla oblongata and pons, and in several nuclei of midbrain and forebrain. Sulfatide-storing phagocytes were most frequent in the white matter tracts of aged ASA–/– mice, whereas no widespread demyelination was obvious. Loss of neurons was found in two nuclei of the auditory pathway of aged ASA–/– mice (ventral cochlear nucleus and nucleus of trapezoid body). The distributional pattern of sulfatide storage throughout the CNS of ASA–/– mice largely corresponds to data reported for human MLD. An important difference, however, which remains unexplained at present, is the absence of obvious demyelination from the CNS of ASA–/– mice up to the age of 2 years.
异染性脑白质营养不良神经元的超微结构研究。
影响因子：
1.1
作者：
Peng,L;Suzuki,K
通讯作者：
Suzuki,K