Aberrant astrocytic expression of chondroitin sulfate proteoglycan receptors in a rat model of amyotrophic lateral sclerosis
Aberrant astrocytic expression of chondroitin sulfate proteoglycan receptors in a rat model of amyotrophic lateral sclerosis
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DOI：
10.1002/jnr.24127
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发表时间：
2018-02
影响因子：
4.2
通讯作者：
T. Shijo;H. Warita;N. Suzuki;Y. Kitajima;Kensuke Ikeda;T. Akiyama;H. Ono;S. Mitsuzawa;A. Nishiyama
中科院分区：
文献类型：
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作者：
T. Shijo;H. Warita;N. Suzuki;Y. Kitajima;Kensuke Ikeda;T. Akiyama;H. Ono;S. Mitsuzawa;A. Nishiyama
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种致死性神经退行性疾病。在中枢神经系统（CNS）中，运动神经元的进行性和全身性丧失伴神经胶质增生是ALS的神经病理学标志。硫酸软骨素蛋白聚糖（CSPGs）是哺乳动物中枢神经系统细胞外基质的主要成分，通过参与胶质瘢痕的形成，抑制轴突再生。最近，发现蛋白酪氨酸磷酸酶σ（PTPσ）和白细胞共同抗原相关蛋白作为CSPG受体在抑制再生中起作用。在这里，我们研究了CSPG受体在转基因雌性大鼠中的表达，这些大鼠过度表达ALS连锁突变的胞质Cu/Zn超氧化物歧化酶基因（SOD 1）。与对照组相比，多种免疫荧光分析显示CSPG受体的异常表达主要在反应性星形胶质细胞中，而ALS转基因大鼠脊髓腹角神经元中的PTPσ表达减少。CSPG受体和反应性星形胶质细胞本身的异常和进行性星形胶质细胞表达可能是在神经退行性疾病（如ALS）下重建再生支持微环境的治疗靶点。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Progressive and systemic loss of motor neurons with gliosis in the central nervous system (CNS) is a neuropathological hallmark of ALS. Chondroitin sulfate proteoglycans (CSPGs) are the major components of the extracellular matrix of the mammalian CNS, and they inhibit axonal regeneration physically by participating to form the glial scar. Recently, protein tyrosine phosphatase sigma (PTPσ) and leukocyte common antigen‐related protein were discovered as CSPG receptors that play roles in inhibiting regeneration. Here we examined the expression of CSPG receptors in transgenic female rats overexpressing an ALS‐linked mutant cytosolic Cu/Zn superoxide dismutase gene (SOD1). In contrast to controls, multiple immunofluorescence analyses revealed aberrant expression of CSPG receptors dominantly in reactive astrocytes, while PTPσ expression in neurons decreased in the spinal ventral horns of ALS transgenic rats. The aberrant and progressive astrocytic expression of CSPG receptors and reactive astrocytes themselves may be therapeutic targets for reconstructing a regeneration‐supportive microenvironment under neurodegenerative conditions such as ALS.