CD24 expression does not affect dopamine neuronal survival in a mouse model of Parkinson's disease

Parkinson’s disease (PD) is a progressive neurodegenerative condition that is characterised by the loss of specific populations of neurons in the brain. The mechanisms underlying this selective cell death are unknown but by using laser capture microdissection, the glycoprotein, CD24 has been identified as a potential marker of the populations of cells that are affected in PD. Using in situ hybridization and immunohistochemistry on sections of mouse brain, we confirmed that CD24 is robustly expressed by many of these subsets of cells. To determine if CD24 may have a functional role in PD, we modelled the dopamine cell loss of PD in Cd24 mutant mice using striatal delivery of the neurotoxin 6-OHDA. We found that Cd24 mutant mice have an anatomically normal dopamine system and that this glycoprotein does not modulate the lesion effects of 6-OHDA delivered into the striatum. We then undertook in situ hybridization studies on sections of human brain and found—as in the mouse brain—that CD24 is expressed by many of the subsets of the cells that are vulnerable in PD, but not those of the midbrain dopamine system. Finally, we sought to determine if CD24 is required for the neuroprotective effect of Glial cell-derived neurotrophic factor (GDNF) on the dopaminergic nigrostriatal pathway. Our results indicate that in the absence of CD24, there is a reduction in the protective effects of GDNF on the dopaminergic fibres in the striatum, but no difference in the survival of the cell bodies in the midbrain. While we found no obvious role for CD24 in the normal development and maintenance of the dopaminergic nigrostriatal system in mice, it may have a role in mediating the neuroprotective aspects of GDNF in this system.帕金森病（Parkinson’s disease, PD）是一种进行性神经退行性病症，以大脑内特定神经元群体的丢失为特征。这种选择性细胞死亡的潜在机制尚不明确，但通过激光捕获显微切割（laser capture microdissection）技术，糖蛋白CD24已被确定为帕金森病受累细胞群体的潜在标志物。我们通过对小鼠脑组织切片进行原位杂交（in situ hybridization）与免疫组织化学（immunohistochemistry）实验，证实CD24在众多上述细胞亚群中均呈高表达。为探究CD24在帕金森病中是否发挥功能性作用，我们通过向纹状体递送神经毒素6-羟基多巴胺（6-OHDA），在Cd24突变小鼠中构建了帕金森病多巴胺能神经元丢失模型。研究发现，Cd24突变小鼠的多巴胺能系统解剖结构正常，且该糖蛋白并不会对纹状体递送的6-OHDA所引发的损伤效应产生调控作用。随后我们对人脑组织切片开展原位杂交实验，结果与小鼠脑组织中的情况一致：CD24在帕金森病易受累的众多细胞亚群中均有表达，但在中脑多巴胺能系统的细胞中无表达。最后，我们旨在明确CD24是否参与介导胶质细胞源性神经营养因子（Glial cell-derived neurotrophic factor, GDNF）对黑质纹状体多巴胺能通路的神经保护作用。实验结果显示，在CD24缺失的情况下，GDNF对纹状体多巴胺能神经纤维的保护作用有所减弱，但对中脑神经元胞体的存活无显著影响。尽管我们未发现CD24在小鼠多巴胺能黑质纹状体系统的正常发育与维持过程中发挥明显作用，但该蛋白可能参与介导GDNF对该系统的神经保护效应。