Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore 560029, Karnataka, India.
Neurosci Lett. 2010 Mar 31;473(1):56-61. doi: 10.1016/j.neulet.2010.02.022. Epub 2010 Feb 17.
We have earlier shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients' produces selective degeneration of motor neurons, both in vitro as well as in vivo. The present study further evaluates the effect of ALS-CSF on the astrocytes in embryonic rat spinal cord cultures. We quantified the number of flat and process-bearing astrocytes in spinal cord cultures exposed to ALS-CSF and compared them against controls. In addition, GFAP and S100beta expression were quantified by Western blot and measurement of immunofluorescence intensity respectively. We found higher number of process-bearing astrocytes in the cultures exposed to ALS-CSF. Both these proteins increased significantly in cultures exposed to ALS-CSF. Our results provide evidence that astroglia respond to toxic factor(s) present in ALS-CSF by undergoing morphological transformation from flat to process bearing which is further confirmed by elevated expression of GFAP and S100beta. The above changes could possibly alter the microenvironment hastening the motor neuron degeneration.
我们之前已经证明,肌萎缩侧索硬化症(ALS)患者的脑脊液(CSF)可导致运动神经元选择性退化,无论是在体外还是体内。本研究进一步评估了 ALS-CSF 对胚胎大鼠脊髓培养中的星形胶质细胞的影响。我们定量分析了暴露于 ALS-CSF 的脊髓培养物中扁平状和有突起的星形胶质细胞的数量,并与对照组进行比较。此外,通过 Western blot 定量测定 GFAP 和 S100beta 的表达,并分别测量免疫荧光强度。我们发现暴露于 ALS-CSF 的培养物中具有更多突起的星形胶质细胞。这两种蛋白在暴露于 ALS-CSF 的培养物中均显著增加。我们的结果提供了证据,表明星形胶质细胞通过从扁平状向具有突起的形态转变来对 ALS-CSF 中存在的毒性因子做出反应,这进一步通过 GFAP 和 S100beta 的表达升高得到证实。上述变化可能会改变微环境,加速运动神经元退化。