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

移植的嗜铬细胞分化为多巴胺能神经元的机制。

基本信息

批准号：
62570054
负责人：
NISHINO Hitoo
金额：
$ 1.15万
依托单位：
Nagoya City University Medical School (1988)Toyama Medical and Pharmaceutical University (1987)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

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.

将儿茶素胺能细胞（多巴胺能、去甲肾上腺素能和嗜铬细胞）移植到单侧6-OHDA损毁黑质纹状体多巴胺通路的大鼠体内，观察其运动障碍的恢复、细胞生长、多巴胺转换以及神经节苷脂的影响.在多巴胺能细胞移植后超过90%的动物中观察到运动恢复。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。使用微透析，发现多巴胺恢复到几乎控制水平，DOPAC和HVA恢复到控制的三分之一。2.移植蓝斑去甲肾上腺素能神经元后，约40%的动物观察到运动恢复。少数TH阳性、多巴胺β羟化酶（DBH）阴性细胞仅存活于轨道边缘。运动恢复与6-OHDA损伤和移植之间的时间长度相关。多巴胺恢复到50%，DOPAC和HVA恢复到对照水平的三分之一。提示去多巴胺神经支配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.移植嗜铬细胞后，不到30%的动物表现出运动恢复。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没有影响。为了改善移植细胞的存活和运动恢复，有必要调节移植细胞的微环境。e.星形胶质细胞活化或内源性营养因子增加。这项研究正在进行之中。4.神经节苷脂促进移植多巴胺能细胞的发育和运动功能的恢复，因此可能是一个强有力的候选中枢神经系统向性因子。