Jollivet Christophe, Aubert-Pouessel Anne, Clavreul Anne, Venier-Julienne Marie-Claire, Montero-Menei Claudia N, Benoit Jean-Pierre, Menei Philippe
INSERM ERIT-M 0104, Bâtiment IBT, 10 rue Andre Boquel, 49100 Angers, France.
Neurosci Lett. 2004 Feb 19;356(3):207-10. doi: 10.1016/j.neulet.2003.11.051.
Glial cell line-derived neurotrophic factor (GDNF) offers the possibility to stimulate axonal regeneration of mesencephalic dopaminergic neurons, which are affected in Parkinson's disease. Nevertheless, a safe and efficient GDNF delivery system that may be used in clinical trials is still lacking. In a previous study, we showed that GDNF-releasing microspheres can deliver the neurotrophic factor for 2 months, allowing in a partial rat model of Parkinson's disease a sprouting of the preserved dopaminergic fibers and functional improvement 8 weeks after the treatment. The present study confirms these previous observations and shows that the amphetamine-induced rotation score is still decreased 24 weeks after the end of GDNF delivery. Nevertheless, the improvement was not statistically significant at the latest time point due to the spontaneous reinnervation observed in the model used.
胶质细胞源性神经营养因子(GDNF)为刺激帕金森病中受影响的中脑多巴胺能神经元的轴突再生提供了可能性。然而,目前仍缺乏一种可用于临床试验的安全有效的GDNF递送系统。在先前的一项研究中,我们表明释放GDNF的微球能够在2个月内递送神经营养因子,在帕金森病部分大鼠模型中,治疗后8周可使保留的多巴胺能纤维发生芽生并改善功能。本研究证实了先前的这些观察结果,并表明在GDNF递送结束24周后,苯丙胺诱导的旋转评分仍有所降低。然而,由于所用模型中观察到的自发再支配现象,在最新时间点改善并无统计学意义。