Phenotypic Plasticity of Grafted Catecholaminergic Neurons and its Regulatory Mechanisms.

1. 采用半帕金森病模型大鼠，研究多巴胺能细胞移植后功能恢复的机制。我们发现：1)TH mRNA/TH阳性细胞存活，2)多巴胺合成/释放增加，3)突触连接，4)多巴胺转运体恢复，5)D_1和D_2受体结合正常化。牛总神经节苷脂（tGS）、唾液酰胆固醇（神经节苷类似物）、IL-6 （B细胞刺激细胞因子）促进了移植多巴胺能细胞的发育/生长，促进了运动恢复。3.1)移植的染色质（肾上腺素能）细胞在多巴胺缺失纹状体中转化为多巴胺能神经元，2)移植的去甲肾上腺素能细胞在多巴胺缺失纹状体中转化为多巴胺能细胞，而在侧脑室中不转化为多巴胺能细胞。3)多巴胺能神经元在多巴胺缺失纹状体中比在正常纹状体或皮质中生长得更好；4)移植的胆碱能神经元在正常纹状体和多巴胺缺失纹状体中生长的方式相似；5)共培养的中脑神经元（部分多巴胺能神经元）向多巴胺缺失纹状体延伸的神经突比向完整纹状体组织延伸的神经突更快。这些证据表明多巴胺缺失纹状体中多巴胺能神经元的某些营养因子的合成/释放增加。在多巴胺缺失纹状体组织的可溶性部分中，一些酸性蛋白增加。这些蛋白的纯化/鉴定正在进行中。

1. Using model rats of hemi-parkinson's disease, the mechanisms of functional recovery after grafting of dopaminergic cells were investigated. We found : 1) the survival of TH mRNA/TH positive cells, 2) increase of dopamine synthesis/release, 3) synaptic connections, 4) recovery of dopamine transporter and 5) normalization of D_1 and D_2 receptor-bindings.2. Bovine total ganglioside (tGS), sialosyl cholesterol (ganglioside analogue), IL-6 (B cell stimulating cytokine) facilitated the development/growth of grafted dopaminergic cells, and promoted the motor recovery.3.1) grafted chromaffin (adrenergic) cells transmute to dopaminergic neurons in dopamine-depleted striatum, 2) grafted noradrenergic cells transmute to dopaminergic cells in dopa-mine-depleted striatum but not in the lateral ventricle, 3) dopaminergic neurons grow much better in dopamine-depleted striatum than in normal striatum or the cortex, 4) grafted cholinergic neurons grow in a similar fashion in normal and dopamine-depleted striatum, 5) co-cultured midbrain neurons (partly dopaminergic neurons) extend more neurites faster toward the dopamine-depleted than toward the intact striatal tissue. These evidences suggest the increase in synthesis/release of some trophic factors for dopaminergic neurons in dopamine-depleted striatum.4. In soluble fraction of dopamine-depleted striatal tissue a few acidic proteins increased. The purification/identification of these proteins is under way.