Sullivan A M, Pohl J, Blunt S B
Department of Neurodegenerative Disorders, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Eur J Neurosci. 1998 Dec;10(12):3681-8. doi: 10.1046/j.1460-9568.1998.00378.x.
Growth/differentiation factor 5 is a member of the transforming growth factor beta superfamily, which has neurotrophic and neuroprotective effects on dopaminergic neurons both in vitro and in vivo. Here we investigate the effects of growth/differentiation factor 5 on foetal mesencephalic grafts transplanted into a rat model of Parkinson's disease, and compare them with those of glial cell line-derived neurotrophic factor. Mesencephalic tissue was suspended in solutions containing either growth/differentiation factor 5 or glial cell line-derived neurotrophic factor prior to transplantation into the left striatum of rats with 6-hydroxydopamine lesions of the left medial forebrain bundle. Both proteins enhanced graft-induced compensation of amphetamine-stimulated rotations. Positron emission tomography studies showed that both neurotrophins increased graft-induced recovery of striatal binding of [11C]RTI-121, a marker for dopaminergic nerve terminals. Post mortem analysis at 8 weeks after transplantation showed that both neurotrophins significantly increased the survival of grafted dopaminergic neurons. This study shows that growth/differentiation factor 5 is at least as effective as glial cell line-derived neurotrophic factor in enhancing the survival and functional activity of mesencephalic grafts, and thus is an important candidate for use in the treatment of Parkinson's disease.
生长/分化因子5是转化生长因子β超家族的成员，在体外和体内对多巴胺能神经元均具有神经营养和神经保护作用。在此，我们研究了生长/分化因子5对移植到帕金森病大鼠模型中的胎儿中脑移植物的影响，并将其与胶质细胞系源性神经营养因子的作用进行比较。在移植到左侧内侧前脑束6-羟基多巴胺损伤的大鼠左侧纹状体之前，将中脑组织悬浮于含有生长/分化因子5或胶质细胞系源性神经营养因子的溶液中。两种蛋白质均增强了移植物诱导的对苯丙胺刺激旋转的代偿作用。正电子发射断层扫描研究表明，两种神经营养因子均增加了移植物诱导的纹状体中[11C]RTI-121（一种多巴胺能神经末梢标记物）结合的恢复。移植后8周的尸检分析表明，两种神经营养因子均显著增加了移植的多巴胺能神经元的存活。本研究表明，生长/分化因子5在增强中脑移植物的存活和功能活性方面至少与胶质细胞系源性神经营养因子一样有效，因此是用于治疗帕金森病的重要候选物。
