Gopinath G, Shetty A K, Tandon P N
Department of Anatomy, All India Institute of Medical Sciences, New Delhi.
Neuroscience. 1991;40(2):429-43. doi: 10.1016/0306-4522(91)90131-7.
Fetal nigral neurons from 16 and 17 gestational days were transplanted into the intact striatum of adult rat. On different post-transplantation days (30-360 days), the structural and immunohistochemical details of the transplants were studied. The grafted neurons matured and showed phenotypical characteristics comparable to that of normal nigral neurons in adult rats until 180 days. Tyrosine hydroxylase-positive neurons were seen not only in the transplant but also in the adjacent host striatum. Tyrosine hydroxylase-positive fibres were also seen extending for a short distance into the host striatum. A large number of synapses in the transplants were of asymmetric type, containing clear round vesicles. These synapses resembled the few intrinsic type present in the normal substantia nigra. On the other hand, the predominant type 2 synapses with pleomorphic vesicles in the normal nigra were infrequently encountered in the transplants. On the 300th day, the cytoplasm of a few of the neurons showed ageing changes in the form of clear spaces, paucity of organelles especially rough endoplasmic reticulum, membrane-bound vacuoles and increase in the lipofuscin population. In addition, localized thickening of the soma and the dendrites were seen in relation to randomly distributed neurons. By 360 days, more than one quarter (26%) of the total neurons showed these changes indicating ageing. The number per unit volume of normal neurons decreased significantly when compared to the transplants on 60 and 90 days. In the substantia nigra of age-matched control, except for an increase in the lysosomal population, other ageing changes were not detectable. The neurons of intact substantia nigra of the host rat, chronologically 4-8 months older than the transplanted neurons, also appeared normal but for lipofuscin granules. The present study provides morphological evidence for rapid ageing of neurons in the long term nigral transplants. These observations raise fresh doubts regarding permanent survival of grafted neurons in the host brain. Studies so far conducted are after prior nigral lesions. Trophic factors following lesions of the host tissue may have influenced the long term survival of the transplanted neurons. On the other hand, such changes may have been missed since no detailed morphological investigations of the long term transplants have been done so far.
将妊娠16和17天的胎儿黑质神经元移植到成年大鼠完整的纹状体中。在移植后的不同天数（30 - 360天），对移植体的结构和免疫组织化学细节进行了研究。直到180天，移植的神经元成熟并表现出与成年大鼠正常黑质神经元相当的表型特征。酪氨酸羟化酶阳性神经元不仅在移植体中可见，在相邻的宿主纹状体中也可见。酪氨酸羟化酶阳性纤维也可见向宿主纹状体短距离延伸。移植体中的大量突触为不对称型，含有清亮的圆形小泡。这些突触类似于正常黑质中存在的少数固有型突触。另一方面，正常黑质中以多形性小泡为主的2型突触在移植体中很少见到。在第300天，一些神经元的细胞质呈现衰老变化，表现为清亮区、细胞器尤其是粗面内质网减少、膜结合空泡以及脂褐素增多。此外，在随机分布的神经元中可见胞体和树突的局部增粗。到360天时，超过四分之一（26%）的神经元总数出现这些衰老变化。与60天和90天的移植体相比，正常神经元单位体积的数量显著减少。在年龄匹配的对照组黑质中，除了溶酶体数量增加外，未检测到其他衰老变化。宿主大鼠完整黑质的神经元，按时间顺序比移植的神经元大4 - 8个月，除了脂褐素颗粒外也看起来正常。本研究为长期黑质移植中神经元的快速衰老提供了形态学证据。这些观察结果对移植神经元在宿主脑中的永久存活提出了新的疑问。迄今为止进行的研究是在预先存在黑质损伤之后。宿主组织损伤后的营养因子可能影响了移植神经元的长期存活。另一方面，由于迄今为止尚未对长期移植体进行详细的形态学研究，这些变化可能被遗漏了。
