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[移植到恒河猴帕金森病模型中的人类胎儿多巴胺神经元的命运:酪氨酸羟化酶免疫细胞化学研究]

[Fate of human fetal dopamine neurons transplanted into rhesus monkey model of Parkinson's disease: a tyrosine hydroxylase immunocytochemical study].

作者信息

Jiang Z H, Liu Z G, Chen S D, Zhou W B, Cai J, Ni Z M, Zhou C F

机构信息

Shanghai Institute of Physiology, Chinese Academy of Sciences.

出版信息

Sheng Li Xue Bao. 1995 Feb;47(1):31-7.

PMID:7784896
Abstract

To predicate the value of human fetal substantia nigra transplantation in clinical treatment of Parkinson's disease (PD), dissociated cells of substantia nigra from 8-12 week old abortive human fetus were grafted into the neostriatum of 5 adult rhesus monkeys with hemiparkinsonism induced by unilateral injection of MPTP. At 2, 5 and 12 months after transplanting the monkeys were sacrificed for tyrosine hydroxylase (TH) immunocytochemistry to examine the survival and possible synaptic contact of transplanted dopamine (DA) neurons. Transplanted TH immunoreactive cells took a pattern of patches scattered in the neostriatum. Each of the cell patches consisted of 3-10 cells. The TH immunoreactive fiber network was seen in the neostriatum. Electron microscopic survey revealed that TH+ buttons arising from grafted DA neurons formed symmetric or asymmetric synapses with TH- dendritic shafts/spines, and TH+ dendrites were seen to form synapses with TH- axons of the host. Additionally, there were a few synapses formed by TH+ axonal terminals with negative buttons. The results suggest that DA neurons from 8-12 week old abortive human fetus are able to survive grafting into the neostriatum of monkey, a species phylogenetically very close to human, and to establish reciprocal synaptic connectivity with the host even at 2 months post-transplanting. It is, therefore, inferable that embryonic human DA neurons transplanted into human neostriatum may have the same fate as in monkeys.

摘要

为了预测人胎儿黑质移植在帕金森病(PD)临床治疗中的价值,将8 - 12周龄人工流产胎儿的黑质解离细胞移植到5只单侧注射MPTP诱导产生偏侧帕金森病的成年恒河猴的新纹状体中。在移植后2、5和12个月处死猴子,进行酪氨酸羟化酶(TH)免疫细胞化学检测,以检查移植的多巴胺(DA)神经元的存活情况及可能的突触联系。移植的TH免疫反应性细胞呈散在分布于新纹状体的斑块状。每个细胞斑块由3 - 10个细胞组成。在新纹状体中可见TH免疫反应性纤维网络。电子显微镜观察显示,移植的DA神经元产生的TH + 终扣与TH - 树突干/棘形成对称或不对称突触,并且可见TH + 树突与宿主的TH - 轴突形成突触。此外,还有一些由TH + 轴突终末与阴性终扣形成的突触。结果表明,8 - 12周龄人工流产胎儿的DA神经元能够在移植到与人类系统发育关系非常接近的猴子新纹状体后存活,甚至在移植后2个月就能与宿主建立相互的突触连接。因此,可以推断,移植到人类新纹状体中的胚胎人DA神经元可能与在猴子中的命运相同。

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