Bannerman Peter, Hahn Ashleigh, Soulika Athena, Gallo Vittorio, Pleasure David
Institute for Pediatric Regenerative Research, UC Davis School of Medicine, Shriners Hospital for Children, Northern California, Sacramento, California 95817, USA.
Glia. 2007 Jan 1;55(1):57-64. doi: 10.1002/glia.20437.
A prominent feature of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is the accumulation of enlarged, multipolar glial fibrillary acidic protein (GFAP) and brain lipid binding protein (BLBP) immunoreactive astroglia within and at the margins of the inflammatory demyelinative lesions. Whether this astrogliosis is due to both astroglial hyperplasia and hypertrophy or solely to astroglial hypertrophy is controversial. We now report that coincident with the first appearance of inflammation and clinical deficits in mice with myelin oligodendrocyte glycoprotein peptide (MOG peptide)-induced EAE, the radially oriented, bipolar, GFAP, and BLBP positive cells (adult radial glia) present in normal spinal cord white matter undergo mitosis and phenotypic transformation to hypertrophic astroglia. To facilitate visualization of relationships between these hypertrophic astroglia and dying and regenerating oligodendroglia, we used mice that express enhanced green fluorescent protein (EGFP) in cells of the oligodendroglial lineage. During the first week after onset of illness, markedly swollen EGFP+ cells without processes were seen within lesions, whereas EGFP+ cells that expressed immunoreactive cleaved caspase-3 were uncommon. These observations support the hypothesis that necrosis contributes to oligodendroglial loss early in the course of EAE. Later in the illness, EGFP+ cells accumulated amongst hypertrophic astroglia at the margins of the lesions, while the lesions themselves remained depleted of oligodendroglia, suggesting that migration of oligodendroglial lineage cells into the lesions was retarded by the intense perilesional gliosis.
多发性硬化症（MS）和实验性自身免疫性脑脊髓炎（EAE）的一个显著特征是，在炎性脱髓鞘病变内部及边缘，出现了体积增大、呈多极的、胶质纤维酸性蛋白（GFAP）和脑脂质结合蛋白（BLBP）免疫反应阳性的星形胶质细胞聚集。这种星形胶质细胞增生是由于星形胶质细胞的增生和肥大，还是仅仅由于肥大，目前存在争议。我们现在报告，在髓鞘少突胶质细胞糖蛋白肽（MOG肽）诱导的EAE小鼠中，随着炎症和临床缺陷的首次出现，正常脊髓白质中呈放射状排列、双极的、GFAP和BLBP阳性细胞（成年放射状胶质细胞）会发生有丝分裂，并向肥大的星形胶质细胞进行表型转化。为了便于观察这些肥大的星形胶质细胞与正在死亡和再生的少突胶质细胞之间的关系，我们使用了在少突胶质细胞谱系细胞中表达增强型绿色荧光蛋白（EGFP）的小鼠。在发病后的第一周内，在病变中可见明显肿胀的无突起EGFP+细胞，而表达免疫反应性裂解型半胱天冬酶-3的EGFP+细胞并不常见。这些观察结果支持了坏死在EAE病程早期导致少突胶质细胞丢失的假说。在病程后期，EGFP+细胞在病变边缘的肥大星形胶质细胞中聚集，而病变本身仍然缺乏少突胶质细胞，这表明少突胶质细胞谱系细胞向病变中的迁移受到了病变周围强烈胶质细胞增生的阻碍。
