Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease
Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease
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DOI：
10.1007/bf01291789
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发表时间：
1996-01-01
影响因子：
3.3
通讯作者：
Hirsch, EC
中科院分区：
文献类型：
--
作者：
Hunot, S;Bernard, V;Hirsch, EC
胶质细胞源性神经营养因子（GDNF）是一种有效的多巴胺能神经元的神经营养因子。由于多巴胺能神经元在帕金森病中退化，因此该因子是一种潜在的治疗工具，可以在病理过程中挽救多巴胺能神经元。此外，GDNF表达减少可能参与疾病的病理生理学。在这项研究中，我们测试了是否GDNF的产生改变可能参与这种疾病的细胞死亡机制。GDNF基因表达通过使用对应于人GDNF基因外显子2序列的核糖核酸探针的原位杂交进行分析。实验进行中脑和纹状体的组织切片，从8例帕金森氏病患者和6名对照组相匹配的死亡年龄和死后延迟。在两组患者中均未观察到标记。这种缺乏可检测的表达不能归因于方法学问题，因为使用相同的探针观察到阳性染色的部分星形胶质细胞瘤活检从人类成年人和在死后获得的新生婴儿的大脑的部分。这些数据表明，GDNF可能是在一个非常低的水平表达在成人大脑和其参与帕金森氏病的病理生理学仍有待证明。然而，GDNF可能是治疗帕金森病的一种强有力的新药物。
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.