Labandeira-Garcia J L, Guerra M J
Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Spain.
Brain Res. 1994 Jul 25;652(1):87-97. doi: 10.1016/0006-8993(94)90321-2.
Innervation of intrastriatal grafts of fetal striatal tissue by host corticostriatal projections has been shown in a number of previous studies in rats. In the work reported here, induction of Fos protein in grafted striatal neurons by electrical stimulation of the host frontoparietal cortex has been used as cell-level marker of corticostriatal postsynaptic responses within the striatal grafts. Unilateral cortical stimulation 30 min before sacrifice led to bilateral widespread and intense Fos induction throughout the normal striatum, although the response was somewhat more intense ipsilaterally and in the dorsolateral rostral striatum. In adult rats whose striatum had been lesioned with ibotenic acid 10-12 days prior to implantation of fetal striatal tissue, 3- and 18-month-old striatal grafts showed Fos immunoreactivity in a considerable number of cells after either bilateral, or ipsilateral (approximately 30-40% of the density of Fos-immunoreactive cells in the normal striatum) or contralateral cortical stimulation. Double-Fos and -DARPP-32 immunohistochemistry revealed that the Fos-immunoreactive nuclei were concentrated in the DARPP-32-positive (i.e. striatum-like) patches, which contained approximately 60% of the density of Fos-positive nuclei in the normal striatum after either ipsilateral or bilateral stimulation. However, Fos-immunoreactive nuclei were unevenly distributed within the DARPP-32-positive compartment of the graft, with some clusters of Fos-immunoreactive nuclei at 2-3 x the density observed in the normal striatum and other areas with Fos-immunoreactive nuclei present at lower density or absent. Fos induction was also observed in 4-week-old grafts, indicating that functional corticostriatal synaptic contacts develop rapidly. Striatal grafts implanted either in non-lesioned host striatum or in long-term (18 months) lesioned striatum, similarly showed Fos-positive nuclei after cortical stimulation, indicating that host corticostriatal fibers are equally capable of establishing functional synaptic contacts under these conditions. These results indicate that host corticostriatal fibres not only form an axonal network within the graft but also induce postsynaptic responses which may contribute to the observed graft-induced amelioration of lesion-derived behavioural deficits.
在以往多项针对大鼠的研究中，已证实宿主皮质纹状体投射对胎儿纹状体组织的纹状体内移植体具有神经支配作用。在本文报道的研究中，通过电刺激宿主额顶叶皮质诱导移植纹状体神经元中的Fos蛋白，以此作为纹状体内移植体中皮质纹状体突触后反应的细胞水平标记。处死前30分钟进行单侧皮质刺激，导致正常纹状体内双侧广泛且强烈的Fos诱导，尽管同侧以及背外侧吻侧纹状体的反应更为强烈。在胎儿纹状体组织植入前10 - 12天用鹅膏蕈氨酸损伤纹状体的成年大鼠中，3个月和18个月大的纹状体移植体在双侧、同侧（约为正常纹状体中Fos免疫反应性细胞密度的30 - 40%）或对侧皮质刺激后，相当数量的细胞显示出Fos免疫反应性。双重Fos和DARPP - 32免疫组织化学显示，Fos免疫反应性细胞核集中在DARPP - 32阳性（即纹状体样）斑块中，同侧或双侧刺激后，这些斑块中Fos阳性细胞核的密度约为正常纹状体的60%。然而，Fos免疫反应性细胞核在移植体的DARPP - 32阳性区域内分布不均一，一些Fos免疫反应性细胞核簇的密度是正常纹状体中观察到密度的2 - 3倍，而其他区域Fos免疫反应性细胞核的密度较低或不存在。在4周龄的移植体中也观察到Fos诱导，表明功能性皮质纹状体突触联系迅速形成。植入未损伤宿主纹状体或长期（18个月）损伤纹状体的纹状体移植体，在皮质刺激后同样显示出Fos阳性细胞核，表明在这些条件下宿主皮质纹状体纤维同样能够建立功能性突触联系。这些结果表明，宿主皮质纹状体纤维不仅在移植体内形成轴突网络，还能诱导突触后反应，这可能有助于观察到的移植体诱导的损伤所致行为缺陷的改善。
