Molander-Melin Marie, Pernber Zarah, Franken Sebastian, Gieselmann Volkmar, Månsson Jan-Eric, Fredman Pam
Institite of Clinical Neuroscience, Experimental Neuroscience Section, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, SE-431 80 Mölndal, Sweden.
J Neurocytol. 2004 Jul;33(4):417-27. doi: 10.1023/B:NEUR.0000046572.53905.2c.
Arylsulfatase A (ASA) degrades sulfatide, seminolipid and lactosylceramide sulfate, glycolipids recognized by the Sulph I antibody although sulfatide is considered the main antigen. Sulfatide is myelin associated but studies have shown a minor distribution also in non-myelin forming cells. The aim of this work was to further study sulfatide in neurons and astrocytes by immunohistochemistry, facilitated by investigation of tissue from adult ASA deficient (ASA -/-) mice. Cells with a low presence of sulfatide might be detected due to lack of ASA activity and accumulation of Sulph I antigens. Sulfatide positive astrocytes and neurons were more numerous and intensely stained in ASA -/- mice, demonstrating a sulfatide accumulation compared to controls. Sulph I staining was especially increased in the molecular layer of cerebellum, in which Purkinje cell dendrites displayed an altered morphology, and in layer IV-VI of cerebral cortex. In hippocampus, immunostaining was found in neuronal cytoplasm in ASA -/- but in nuclear membranes of control mice. We observed a gray matter astrogliosis, which appeared to be associated to sulfatide accumulation. In addition, the developmental change (<20 months) of Sulph I antigens, galactosylceramide, phospholipids and cholesterol were followed by lipid analyses which verified sulfatide and seminolipid accumulation in adult ASA -/- mice, although no lactosylceramide sulfate could be detected. In addition to demonstrating sulfatide in neurons and astrocytes, this study supports the value of ASA -/- mice as a model for metachromatic leukodystrophy and suggests that accumulation of sulfatide beyond myelin might contribute to the pathology of this disease.
芳基硫酸酯酶A（ASA）可降解硫苷脂、半乳糖脑苷脂硫酸酯和乳糖基神经酰胺硫酸酯，这些糖脂可被Sulph I抗体识别，尽管硫苷脂被认为是主要抗原。硫苷脂与髓磷脂相关，但研究表明在非髓磷脂形成细胞中也有少量分布。本研究的目的是通过免疫组织化学进一步研究神经元和星形胶质细胞中的硫苷脂，借助对成年ASA缺陷（ASA -/-）小鼠组织的研究来实现。由于缺乏ASA活性和Sulph I抗原的积累，可能会检测到硫苷脂含量低的细胞。与对照组相比，ASA -/-小鼠中硫苷脂阳性的星形胶质细胞和神经元数量更多且染色更强，表明存在硫苷脂积累。Sulph I染色在小脑分子层尤其增加，其中浦肯野细胞树突形态发生改变，在大脑皮层IV - VI层也增加。在海马体中，ASA -/-小鼠的免疫染色出现在神经元细胞质中，而对照小鼠出现在核膜上。我们观察到灰质星形胶质细胞增生，这似乎与硫苷脂积累有关。此外，通过脂质分析追踪了Sulph I抗原、半乳糖基神经酰胺、磷脂和胆固醇的发育变化（<20个月），证实成年ASA -/-小鼠中存在硫苷脂和半乳糖脑苷脂硫酸酯积累，尽管未检测到乳糖基神经酰胺硫酸酯。除了在神经元和星形胶质细胞中证明硫苷脂的存在外，本研究支持将ASA -/-小鼠作为异染性脑白质营养不良模型的价值，并表明髓磷脂外硫苷脂的积累可能导致该疾病的病理变化。
