Liste I, Caruncho H J, Guerra M J, Labandeira-Garcia J L
Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Spain.
Brain Res Dev Brain Res. 1997 Nov 12;103(2):185-94. doi: 10.1016/s0165-3806(97)81794-4.
Expression of the alpha1, alpha2 and beta2/3 GABA(A) receptor subunits in maturing cell-suspension striatal grafts and in normal developing striatum was studied by immunocytochemistry. During normal postnatal development, the alpha1 subunit was present in the striatum only at very low density, while the alpha2 and beta2/3 subunits were present with a patchy distribution, in some patches at high density. Double-staining techniques indicated that DARPP-32 (a marker of striatal projection neurons) was not colocalized with alpha1, but was present in some beta2/3-positive areas and all alpha2-positive areas. In striatal grafts, alpha1 immunoreactivity was first detected 2 weeks post-grafting (p.g.), and by 3-10 weeks p.g. the pattern was similar to that observed in mature grafts (1 year p.g.), in which alpha1-immunopositive patches surrounding DARPP-32-positive (i.e. striatum-like) areas are observed. Alpha2 and beta2/3 immunoreactivity was observed within the first week p.g., and by 3-10 weeks p.g. was similar to that observed in mature grafts (i.e. immunoreactivity throughout the graft but with patches of different intensity). During graft maturation there was a marked decline in alpha2 immunoreactivity in DARPP-32-negative areas, as is observed during normal development of the globus pallidus and ventral pallidum. Interestingly, alpha1- and beta2/3-positive fibers (perhaps mostly dendrites) entered DARPP-32-positive patches from DARPP-32-negative areas. This study indicates that the time course of expression of GABA(A) receptor subunits in grafted striatal neurons, closely matches that of morphological maturation of the transplant, that of the development of functional synaptic activity and that of GABA(A) receptor subunit immunoreactivity in normal developing striatum. Our results also suggest that there are significant interactions between DARPP-32-positive and DARPP-32-negative areas with respect to the expression of GABA(A) receptors, and support the suggestion that miniature 'striatopallidal systems' may develop within grafts; such interactions may be important for the functional integration of striatal grafts with the host brain.
通过免疫细胞化学方法研究了α1、α2和β2/3 GABA(A)受体亚基在成熟的细胞悬浮纹状体移植组织以及正常发育的纹状体中的表达情况。在出生后的正常发育过程中，α1亚基在纹状体中的密度极低，而α2和β2/3亚基呈斑片状分布，某些斑块中密度较高。双重染色技术表明，DARPP - 32（纹状体投射神经元的标志物）与α1不共定位，但存在于一些β2/3阳性区域和所有α2阳性区域。在纹状体移植组织中，移植后2周首次检测到α1免疫反应性，到移植后3 - 10周，其模式与成熟移植组织（移植后1年）中观察到的相似，即在围绕DARPP - 32阳性（即纹状体样）区域观察到α1免疫阳性斑块。α2和β2/3免疫反应性在移植后第一周内即可观察到，到移植后3 - 10周与成熟移植组织中观察到的相似（即整个移植组织都有免疫反应性，但强度不同的斑块）。在移植组织成熟过程中，DARPP - 32阴性区域的α2免疫反应性显著下降，这与苍白球和腹侧苍白球正常发育过程中观察到的情况相同。有趣的是，α1和β2/3阳性纤维（可能主要是树突）从DARPP - 32阴性区域进入DARPP - 32阳性斑块。这项研究表明，移植的纹状体神经元中GABA(A)受体亚基的表达时间进程与移植组织的形态成熟、功能突触活动的发育以及正常发育纹状体中GABA(A)受体亚基免疫反应性的时间进程密切匹配。我们的结果还表明，在GABA(A)受体表达方面，DARPP - 32阳性和阴性区域之间存在显著相互作用，并支持在移植组织内可能形成微型“纹状体苍白球系统”的观点；这种相互作用可能对纹状体移植组织与宿主脑的功能整合很重要。
