Caumont Anne-Sophie, Octave Jean-Noël, Hermans Emmanuel
Laboratoire de Pharmacologie Expérimentale (FARL), Université catholique de Louvain, Avenue Hippocrate 54.10, 1200 Bruxelles, Belgium.
Neurosci Lett. 2006 Feb 20;394(3):196-201. doi: 10.1016/j.neulet.2005.10.027. Epub 2005 Nov 18.
Aminoadamantanes are commonly used in the treatment of Parkinson's and Alzheimer's diseases. While these drugs are shown to antagonise ionotropic glutamate receptors on neuronal cells, additional mechanisms could contribute to their neuroprotective properties. The aim of the present study was to investigate the effect of aminoadamantanes on the production of the glial cell line-derived neurotrophic factor (GDNF) in glial cells. For this purpose, we measured the modulation of GDNF release in C6 glioma cell cultures treated for 24 h with amantadine and memantine. Both drugs dose-dependently increased GDNF level in the culture medium with similar potency (submicromolar range) and efficacy (three to four-fold induction). RT-PCR studies revealed that both compounds also increased GDNF mRNA levels and their influence on the GDNF gene transcription was further evidenced using a rat GDNF promoter luciferase reporter assay. Together, these results demonstrate that the neuroprotective effect of amantadine and memantine could involve the regulation of GDNF production by glial cells.
金刚烷胺常用于治疗帕金森病和阿尔茨海默病。虽然这些药物已显示可拮抗神经元细胞上的离子型谷氨酸受体，但其他机制可能也有助于其神经保护特性。本研究的目的是探讨金刚烷胺类药物对神经胶质细胞中胶质细胞源性神经营养因子（GDNF）产生的影响。为此，我们测量了用金刚烷胺和美金刚处理24小时的C6胶质瘤细胞培养物中GDNF释放的调节情况。两种药物均以剂量依赖性方式增加了培养基中的GDNF水平，其效力（亚微摩尔范围）和效果（诱导三到四倍）相似。逆转录聚合酶链反应（RT-PCR）研究表明，这两种化合物还增加了GDNF mRNA水平，并且使用大鼠GDNF启动子荧光素酶报告基因测定法进一步证明了它们对GDNF基因转录的影响。总之，这些结果表明金刚烷胺和美金刚的神经保护作用可能涉及神经胶质细胞对GDNF产生的调节。
