Long-term survival of grafted cells, dopamine synthesis/release, synaptic connections, and functional recovery after transplantation of fetal nigral cells in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway
Long-term survival of grafted cells, dopamine synthesis/release, synaptic connections, and functional recovery after transplantation of fetal nigral cells in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway
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黑质纹状体多巴胺通路单侧 6-OHDA 损伤大鼠胎儿黑质细胞移植后移植细胞的长期存活、多巴胺合成/释放、突触连接和功能恢复
DOI：
10.1016/0006-8993(90)90115-r
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Sadao Shiosaka
中科院分区：
文献类型：
--
作者：
H. Nishino;T. Hashitani;M. Kumazaki;Haruhiko Sato;F. Furuyama;Y. Isobe;N. Watari;M. Kanai;Sadao Shiosaka
在半侧帕金森病动物模型中，观察移植的黑质细胞的存活、突触连接、多巴胺(DA)的合成/释放和运动障碍的恢复，并在移植后3个月、1年和2年饲养3组动物。将胎儿黑质DA能细胞悬液移植到黑质纹状体DA通路单侧6-OHDA损毁大鼠的同侧尾状核内。通过甲基苯丙胺诱导的旋转评估，运动障碍在移植后第2周部分恢复，在移植后第4周显著恢复，此后保持稳定。沿移植轨迹可检测到大量酪氨酸羟化酶(TH)阳性细胞。TH阳性细胞数在3组动物中相似。这些TH阳性细胞在宿主尾状核内形成突触联系。通过体内微透析检测，移植部位周围的细胞外多巴胺、二羟基苯乙酸(DOPAC)和高香草酸(HVA)恢复到对照组的30-100%。3组动物之间DA、DOPAC和HVA浓度无显著差异。它们对甲基苯丙胺负荷也有反应，尽管幅度较小。用TH基因探针进行原位杂交放射自显影分析，发现TH阳性细胞表达TH基因。数据表明，移植的胎儿DAR能细胞存活、合成和释放。DA，在宿主大脑中建立突触连接，并改善运动障碍超过2年。移植后2年，3组动物的上述指标均无明显差异，无不良反应发生。因此，证实了神经细胞移植到脑内是一种很有前途的恢复受损功能的方法。
In animal models of hemi-Parkinson's disease, survival of grafted nigral cells, their synaptic connections, dopamine (DA) synthesis/release, and recovery from motor disturbances were investigated, and these were compared among 3 groups of animals raised for 3 months, 1 year and 2 years after the transplantation. Fetal nigral DAergic cell suspensions were transplanted in the ipsilateral caudate nucleus of rats with unilateral 6-OHDA lesions in the nigrostriatal DA pathway. Motor disturbances, assessed by methamphetamine-induced rotation, recovered partly in the 2nd week, significantly in the 4th week after the grafting, and remained stable thereafter. Many tyrosine hydroxylase (TH)-positive cells were detected along the grafting tracks. The number of TH-positive cells was similar in the 3 groups of animals. These TH-positive cells made synaptic connections in the host caudate. By in vivo microdialysis measurement, extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) around the grafted sites recovered to 30–100% of those of controls. No significant differences were observed in the concentration of DA, DOPAC and HVA among 3 groups of animals. They also responded to methamphetamine loading though the magnitudes were smaller. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in in situ hybridization-autoradiographic analysis. Data indicate that grafted fetal DAergic cells survive, synthesize and release. DA, make synaptic connections in the host brain and ameliorate motor disturbances for over 2 years. There were no differences in these parameters among the 3 groups of animals, and no untoward side effects were observed event at 2 years after the grafting. Thus it was confirmed that the grafting of neuronal cells into the brain is a promising approach to restore disturbed function.