Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, PR China.
Life Sci. 2011 Sep 12;89(11-12):355-63. doi: 10.1016/j.lfs.2011.06.028. Epub 2011 Jul 20.
The objective of this study is to prove that activation of astrocytes precedes neuron cell death in the neurodegenerative process induced by d-galactose (d-gal) exposure.
Male adult mice were given intraperitoneal injection of d-gal (200 mg/kg per day) for 2 weeks. The whole brain homogenate and hippocampal sections were then prepared for biochemical analyses, immunohistochemistry and electron microscopy, respectively.
There were no statistically significant differences in brain oxidative and antioxidative parameters between d-gal-treated mice and saline controls. There was also lack of morphological impairment in hippocampal neuronal soma, dendrites and synapses in the model mice. In contrast, hippocampal astrocytes were dramatically activated, and perisynaptic processes of astrocytes were swelling as revealed by ultrastructural analysis. Moreover, d-gal-treated group showed increases in immunostaining levels of glutamate transporter-1 and aquaporin-4 in the hippocampus, which might increase uptake of glutamate from the synaptic cleft into astrocytes.
These results reveal that astrocytes undergo structural and biochemical changes while no impairment of neuronal elements occurs after 2 weeks of d-gal exposure. Thus, targeting astrocytes may be a promising strategy for the treatment of neurodegenerative diseases at the early stages.
本研究旨在证明星形胶质细胞的激活先于半乳糖（d-gal）暴露诱导的神经退行性过程中的神经元细胞死亡。
雄性成年小鼠接受腹腔注射 d-gal（每天 200mg/kg）2 周。然后分别制备全脑匀浆和海马切片，用于生化分析、免疫组织化学和电子显微镜检查。
d-gal 处理组和生理盐水对照组之间的大脑氧化和抗氧化参数没有统计学上的显著差异。模型小鼠海马神经元体、树突和突触也没有形态损伤。相比之下，海马星形胶质细胞被显著激活，并且超微结构分析显示星形胶质细胞的突触旁过程肿胀。此外，d-gal 处理组在海马中谷氨酸转运体-1 和水通道蛋白-4 的免疫染色水平增加，这可能增加从突触间隙摄取谷氨酸进入星形胶质细胞。
这些结果表明，在暴露于 d-gal 2 周后，星形胶质细胞发生结构和生化变化，而神经元成分没有损伤。因此，靶向星形胶质细胞可能是治疗神经退行性疾病早期的一种有前途的策略。
