Li Jiao, Lu Yi, Liang Huiting, Tang Chunyan, Zhu Lei, Zhang Jie, Xu Renshi
Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.; Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China.
Int J Biol Sci. 2016 Sep 14;12(10):1181-1190. doi: 10.7150/ijbs.16158. eCollection 2016.
In order to searching the possible pathogenesis of amyotrophic lateral sclerosis (ALS), we examined the expression and distribution of FUS/TLS protein in the different anatomic regions, segments and neural cells of adult spinal cord at the different stages of the SOD1 wild-type and G93A transgenic mice using the fluorescent immunohistochemistry. Result revealed that, in the SOD1 wild-type mice, the FUS/TLS expression almost wasn't detected. However, in the SOD1 G93A mice, the FUS/TLS expression in the white matter was significantly more than that in the gray matter. In the white matter, the FUS/TLS expression in the anterior funiculus was more than that in the lateral funiculus more than that in the posterior funiculus. In the gray matter, the FUS/TLS expression in the ventral horn was more than that surrounding the central canal more than that in the dorsal horn. The FUS/TLS expression in the thoracic segment was more than that in the cervical segment more than that in the lumbar segment. Almost all FUS/TLS expressed in the nuclear of the GFAP positive cell at the onset stage, but it expressed in both the nuclear and the cytoplasm of the GFAP positive cell at the progression stage, almost didn't detected FUS/TLS expression in the NeuN and Oligo positive cells. The FUS/TLS expression was positively correlated with the neuron death. Our data suggested that the expressive increase and mislocalization of FUS/TLS in the astrocyte cell might cause the motor neuron degenerative death in the SOD1 G93A transgenic mice.
为了探寻肌萎缩侧索硬化症（ALS）的可能发病机制，我们运用荧光免疫组织化学方法，检测了超氧化物歧化酶1（SOD1）野生型和G93A转基因小鼠成年脊髓不同解剖区域、节段及神经细胞中FUS/TLS蛋白的表达及分布情况。结果显示，在SOD1野生型小鼠中，几乎未检测到FUS/TLS表达。然而，在SOD1 G93A小鼠中，白质中的FUS/TLS表达显著高于灰质。在白质中，前索中的FUS/TLS表达高于外侧索，外侧索又高于后索。在灰质中，腹角中的FUS/TLS表达高于中央管周围，中央管周围又高于背角。胸段的FUS/TLS表达高于颈段，颈段高于腰段。在发病初期，几乎所有FUS/TLS都表达于GFAP阳性细胞的细胞核中，但在进展期，它表达于GFAP阳性细胞的细胞核和细胞质中，在NeuN和Oligo阳性细胞中几乎未检测到FUS/TLS表达。FUS/TLS表达与神经元死亡呈正相关。我们的数据表明，星形胶质细胞中FUS/TLS表达增加及定位错误可能导致SOD1 G93A转基因小鼠运动神经元退行性死亡。
