ABNORMAL ASTROCYTE DIFFERENTIATION AND DEFECTIVE CELLULAR INTERACTIONS IN WOBBLER MOUSE SPINAL-CORD
ABNORMAL ASTROCYTE DIFFERENTIATION AND DEFECTIVE CELLULAR INTERACTIONS IN WOBBLER MOUSE SPINAL-CORD
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DOI：
10.1007/bf01181559
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发表时间：
1994-03-01
期刊：
影响因子：
--
通讯作者：
RIEGER, F
中科院分区：
文献类型：
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作者：
HANTAZAMBROISE, D;BLONDET, B;RIEGER, F
wobbler突变是一种常染色体隐性遗传性状，在出生后早期发育中表现出与运动神经元变性相关的肌肉萎缩。研究表明，摇摆小鼠脊髓中胶质原纤维酸性蛋白（GFAP）水平显著升高。我们采用免疫细胞化学分析结合共聚焦显微镜研究了gap阳性星形胶质细胞在疾病过程中在摇摆鼠脊髓中的发育分布，以及在成年摇摆鼠脊髓星形胶质细胞的原代培养中。产后1 ~ 10个月，wobbler小鼠的星形胶质细胞的数量和分布发生了许多变化，到1个月时，前角出现少量强gmap阳性的星形胶质细胞。它们的数量增加，在2-10个月时在整个脊髓灰质和白质中观察到。这些反应性星形胶质细胞具有厚、短、广泛分支的突起，与对照小鼠中观察到的长、无分支的突起形成对比。摇摆星形胶质细胞突起垂直于脊髓表面，这与正常的平行同心方向形成对比。星形胶质细胞突起无扩张，从白质向灰质出口。此外，脑膜下的摆动脊髓表面显示交错突，端足和扁平的星形胶质细胞细胞体的显著减少，形成了一个混乱的层。在体外，突变的星形胶质细胞具有与体内相似的形态特征，特别是发育出短、粗、分枝的突起。这些突变的星形胶质细胞在培养物中不相互接触，而正常的成熟培养物在长过程之间显示出细胞-细胞接触的发生率增加。星形胶质细胞反应性的增加与星形胶质细胞过程排列的这些改变相关，可能反映了摇摆病过程中的一个重要的主要事件，而不是对运动神经元死亡的非特异性反应。
The wobbler mutation is inherited as an autosomal recessive trait and displays a muscular atrophy associated with motoneuron degeneration in early postnatal development. It has been shown that the level of glial fibrillary acidic protein (GFAP) is greatly increased in the spinal cord of wobbler mice. We performed immunocytochemical analyses combined with confocal microscopy to study the developmental distribution of GFAP-positive astrocytes in the spinal cord of wobbler mice during the course of the disease, and in primary cultures of adult wobbler spinal cord astrocytes. Many changes in the number and distribution of astrocytes were observed in the wobbler mice from 1-10 months post-partum Strongly GFAP-positive astrocytes are present in small number in the anterior horn by 1 month. They increase in number and are observed in the entire spinal cord grey and white matters by 2-10 months. These reactive astrocytes have thick, short, extensively branched processes which contrast with the long, unbranched processes observed in control mice. The wobbler astrocyte processes are oriented perpendicular to the surface of the spinal cord, which contrasts with the normal parallel, concentric orientation. No expansion of astrocyte processes exit from the white matter towards the grey matter. Moreover, the surface of the wobbler spinal cord beneath the meninges displays a dramatic decrease of interdigitating processes, end feet and flattened cell bodies of astrocytes that form a disorganized layer. In vitro, mutant astrocytes have morphological characteristics similar to those in vivo and, in particular, develop short, thick, branched processes. These mutant astrocytes in cultures do not contact one another, whereas normal mature cultures show an increased incidence of cell-cell contacts between long processes. The increase of astrocyte reactivity associated with these modifications in astrocytic process arrangement may reflect an important primary event in the course of the wobbler disease rather than a non-specific response to motoneuronal death.