The mechanism of differentiation of transplanted chromaffin cells into dopaminergic neurons.

将儿茶酚胺能细胞（多巴胺能细胞、去甲肾上腺素能细胞和染色质细胞）移植到黑质纹状体多巴胺通路单侧6-OHDA损伤大鼠体内，观察其运动障碍的恢复、细胞生长、多巴胺的转换和神经节苷脂的作用。超过90%的动物在多巴胺能细胞移植后运动恢复。许多酪氨酸羟化酶（TH）阳性细胞在移植轨道周围存活，并与宿主神经元元件形成突触接触。微透析治疗后，多巴胺恢复到控制水平，多巴胺和HVA恢复到控制水平的三分之一。2. 移植蓝斑去肾上腺素能神经元后，约40%的动物运动恢复。较少的TH阳性，多巴胺-羟化酶（DBH）阴性细胞仅在轨道边缘存活。运动恢复与6-OHDA病变到移植的时间长短相关。多巴胺恢复了50%，多巴胺和HVA恢复到对照水平的三分之一。提示在多巴胺失神经尾状核中存在促进去甲肾上腺素能细胞向多巴胺能细胞分化的营养因子。3. 不到30%的动物在移植嗜铬细胞后运动恢复。局部或全身给予神经生长因子、白细胞介素-6和神经节苷脂对恢复无影响。为了提高移植物细胞的存活率和运动恢复能力，需要调节移植物细胞的微环境，即星形胶质细胞的激活或内源性营养因子的增加。这样的研究正在进行中。4. 神经节苷脂促进了移植多巴胺能细胞的发育和运动恢复，因此可能是中枢神经系统热带因子的有力候选者之一。

Catecholaminergic cells (dopaminergic, noradrenergic and chromaffin cells) were transplanted into rats with unilateral 6-OHDA lesion in nigrostriatal dopamine pathway, and recovery of motor disturbance, cell growth, dopamine turnover, and effect of ganglioside were investigated.1. Motor recovery was observed in more than 90% of animals following dopaminergic cell grafting. many tyrosine hydroxylase (TH) positive cells survived around the grafting track and made synaptic contacts with host neuronal elements. Using microdialysis it was found that dopamine recovered up to almost control level and DOPAC and HVA to one third of controls. 2. Following grafting of locus coeruleus noradrenergic neurons, motor recovery was observed in about 40% of animals. A fewer TH positive-, dopamine beta hydroxylase (DBH) negative cells survived only on the margin of the track. Motor recovery was correlated with the length of time between 6-OHDA lesion and grafting. Dopamine recovered up to 50% and DOPAC and HVA to one third of control levels. Thus it is suggested that some trophic factor that promotes the differentiation of noradrenergic cells into dopaminergic cells develops and fluctuates in dopamine denervated caudate. 3. Less than 30% of animals showed motor recovery after grafting of chromaffin cells. Local or systemic administration of nerve growth factor, interleukin-6 and ganglioside had no effect on the recovery. To improve the cell survival and motor recovery it is necessary to modulate the microenvironment of the grafted cells i. e. , activation of astroglia or increase of endogenous trophic factors. Such study is under way. 4. Ganglioside facilitated the development of grafted dopaminergic cells and motor recovery, and thus could be one of a strong candidate for CNS tropic factor.