DiFiglia M, Schiff L, Deckel A W
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02114.
J Neurosci. 1988 Apr;8(4):1112-30. doi: 10.1523/JNEUROSCI.08-04-01112.1988.
Behavioral and biochemical studies have suggested that fetal striatal grafts in the adult rat neostriatum can reverse deficits induced by excitotoxic lesions of the host caudate tissue. In this study, fetal day 17-18 striatal grafts were examined at 2, 5-6, 12, and 44-48 weeks following their implantation into saline- or kainic acid-treated host caudate nucleus in order to compare the neuronal organization of the grafts and the host caudate nucleus and to determine whether the differentiation of graft tissue was influenced by the period of implantation or prior lesion of the host caudate nucleus with kainic acid. Compared to host neostriatum, the grafts at the light-microscopic level lacked bundles of myelinated axons and had neurons that were tightly packed in clusters and rich in Nissl substance. Neurons in the grafts were mostly of medium size, had significantly larger cross-sectional areas, and more frequently exhibited indented nuclei than host caudate neurons. At the electron-microscopic level, grafts 2 weeks following implantation contained many features seen in the normally developing neostriatum, such as growth cones, immature synapses, and degenerating profiles. Grafts appeared mature by 5-6 weeks and contained at least 6 types of neurons and 8 types of axon terminals, which formed synapses with cell bodies, dendrites, spines, and axon initial segments. Both symmetric and asymmetric synapses were found within the grafts. The density of synapses was significantly lower in all the transplants than in host tissue, with the exception of the 5-6 week grafts, where values were statistically comparable to host caudate. A significantly higher proportion of axodendritic synapses was present in the graft neuropil than in the caudate nucleus. The lengths of the synaptic junctions in the grafts were the same as those in the neostriatum. There was little qualitative or quantitative difference in synaptic organization between transplants in kainic acid and sham-lesioned host, with grafts in both host treatment conditions exhibiting the same synaptic density and proportion of axodendritic/axospinous synapses. The development of a high differentiated ultrastructure within striatal grafts is consistent with recent anatomical evidence showing interconnections between striatal grafts and host-lesioned caudate nucleus. Although graft neuropil shows striking similarities in neuronal organization to the caudate nucleus, it also exhibits some distinct differences that may have implications for understanding the functional properties of fetal striatal grafts in animal models of Huntington's disease.
行为学和生物化学研究表明，成年大鼠新纹状体中的胎儿纹状体移植能够逆转宿主尾状组织兴奋性毒性损伤所诱导的缺陷。在本研究中，对胎龄17 - 18天的纹状体移植组织在植入生理盐水或 kainic 酸处理的宿主尾状核后的2周、5 - 6周、12周以及44 - 48周进行了检查，以比较移植组织和宿主尾状核的神经元组织，并确定移植组织的分化是否受植入时间或宿主尾状核预先用 kainic 酸损伤的影响。与宿主新纹状体相比，光镜下移植组织缺乏成束的有髓轴突，神经元紧密聚集，尼氏体丰富。移植组织中的神经元大多为中等大小，横截面积显著更大，且核凹陷的情况比宿主尾状核神经元更常见。在电镜水平，植入后2周的移植组织具有正常发育新纹状体中的许多特征，如生长锥、未成熟突触和退变结构。移植组织在5 - 6周时似乎成熟，包含至少6种类型的神经元和8种类型的轴突终末，它们与胞体、树突、棘和轴突起始段形成突触。移植组织内同时存在对称和不对称突触。除了5 - 6周的移植组织，其突触密度在统计学上与宿主尾状核相当外，所有移植组织中的突触密度均显著低于宿主组织。移植组织神经毡中轴突 - 树突突触的比例显著高于尾状核。移植组织中突触连接的长度与新纹状体中的相同。在 kainic 酸处理的宿主和假损伤宿主中的移植组织，在突触组织方面几乎没有定性或定量差异，两种宿主处理条件下移植组织的突触密度以及轴突 - 树突/轴突 - 棘突触的比例相同。纹状体移植组织中高度分化的超微结构的发育与最近的解剖学证据一致，该证据显示纹状体移植组织与宿主损伤的尾状核之间存在相互连接。尽管移植组织神经毡在神经元组织方面与尾状核有显著相似性，但也表现出一些明显差异，这可能对理解亨廷顿病动物模型中胎儿纹状体移植组织的功能特性具有重要意义。
