在帕金森病大鼠模型中，短期给予胶质细胞源性神经营养因子（GDNF）治疗可对受损黑质多巴胺能神经元产生长期挽救作用。
Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease.
作者信息
Winkler C, Sauer H, Lee C S, Björklund A
机构信息
Lund University, Wallenberg Neuroscience Center, Sweden.
出版信息
J Neurosci. 1996 Nov 15;16(22):7206-15. doi: 10.1523/JNEUROSCI.16-22-07206.1996.
Abstract
Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson's disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model.
摘要
胶质细胞源性神经营养因子（GDNF）已被证明在体内对多巴胺（DA）神经元具有神经保护作用。在此，我们报告了在一个大鼠损伤模型中，延迟短期给予GDNF后黑质DA神经元的长期挽救情况，该模型再现了帕金森病中缓慢进展的退行性过程。在黑质附近注射GDNF可提供近乎完全的保护，并且在停止GDNF治疗后，受损的黑质神经元持续存活至少4个月。然而，黑质细胞的长期挽救并未伴随着受损纹状体靶点的任何显著再支配，也未出现药物诱导或自发运动行为功能恢复的任何迹象。我们得出结论，在大鼠帕金森模型中，功能恢复不仅需要保留黑质DA神经元，还需要恢复纹状体DA功能。
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Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease.在帕金森病大鼠模型中，短期给予胶质细胞源性神经营养因子（GDNF）治疗可对受损黑质多巴胺能神经元产生长期挽救作用。
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