DARPP-32-rich zones in grafts of lateral ganglionic eminence govern the extent of functional recovery in skilled paw reaching in an animal model of Huntington's disease
DARPP-32-rich zones in grafts of lateral ganglionic eminence govern the extent of functional recovery in skilled paw reaching in an animal model of Huntington's disease
复制标题
外侧神经节隆起移植物中富含 DARPP-32 的区域控制亨廷顿病动物模型中熟练爪子到达的功能恢复程度
DOI：
10.1016/0306-4522(96)00238-2
复制
发表时间：
1996
期刊：
影响因子：
3.3
通讯作者：
P. Brundin
中科院分区：
文献类型：
--
作者：
N. Nakao;E. Grasbon;H. Widner;P. Brundin
纹状体组织的移植物包括两种不同类型的组织：具有（P-区）和不具有（NP-区）神经元的区域，所述神经元表达纹状体的特征性标记物，例如多巴胺和环AMP调节的磷蛋白，其具有mol.重量为32，000（DARPP-32）。尚不清楚P区是否单独在亨廷顿病动物模型中纹状体移植物的功能效应中起关键作用。本研究旨在确定：（i）DARPP-32阳性神经元在外侧神经节隆起移植物中的产量;（ii）用自旋捕获剂α-苯基-叔丁基硝酮处理移植组织是否能提高植入DARPP-32阳性神经元的存活率;和（iii）移植物中DARPP-32阳性神经元的数量与移植物对爪的功能影响之间的关系。纹状体单侧喹啉酸损伤大鼠的到达能力。将来自大鼠胚胎（胚胎第14天）外侧神经节隆起的分离组织（添加或不添加α-苯基-叔丁基硝酮（3 mM））植入喹啉酸损伤的纹状体。与未损伤的正常动物相比，纹状体病变的大鼠表现出爪到达能力的实质性损害，特别是在病变对侧，从每个爪取回的颗粒数量判断。纹状体内移植引起了显着改善爪达到的能力。在没有α-苯基-叔丁基硝酮处理的移植物中存活的DARPP-32阳性细胞的平均总数估计为115 × 103，这与α-苯基-叔丁基硝酮处理的移植物没有显著差异。爪到达分数与P区的体积和DARPP-32阳性神经元的数量显著相关，但与NP区的体积和移植物的总体积均不相关。结果表明，P区纹状体移植介导移植衍生的功能恢复在一个复杂的任务，如熟练的前肢使用。虽然用α-苯基-叔丁基硝酮进行抗氧化剂处理未能促进移植物存活，但移植物中DARPP-32阳性细胞的产量与功能恢复程度之间的正相关性高度保证了进一步尝试增加移植物中纹状体组分的产量。
Grafts of striatal tissue comprise two different types of tissue: regions with (P-zones) and without (NP-zones) neurons that express markers characteristic of the striatum, such as dopamine- and cyclic AMP-regulated phosphoprotein with a mol. wt of 32,000 (DARPP-32). It remains unclear whether P-zones alone play a crucial role in functional effects of striatal grafts in an animal model of Huntington's disease. The present study has been performed to determine: (i) the yield of DARPP-32-positive neurons in grafts of lateral ganglionic eminence; (ii) whether treatment of graft tissue with the spin-trapping agent α-phenyl-tert-butyl nitrone enhances the survival of implanted DARPP-32-positive neurons; and (iii) the relationship between the number of DARPP-32-positive neurons in the grafts and functional effects of the grafts on paw-reaching ability in rats with unilateral quinolinic acid lesions of the striatum. Dissociated tissue derived from the lateral ganglionic eminence of rat embryos (embryonic day 14), with or without addition of α-phenyl-tert-butyl nitrone (3 mM), was implanted into the quinolinic acid-lesioned striatum. Compared to unlesioned normal animals, rats with striatal lesions showed substantial impairment in paw-reaching ability, particularly on the side contralateral to the lesion, as judged from the number of pellets retrieved by each paw. Intrastriatal grafts gave rise to a significant improvement in paw-reaching ability. The mean total number of surviving DARPP-32-positive cells in grafts without α-phenyl-tert-butyl nitrone treatment was estimated at 115 × 103, which did not significantly differ from that in α-phenyl-tert-butyl nitrone-treated grafts. The paw-reaching scores were significantly correlated with the volumes of P-zones and the number of DARPP-32-positive neurons, but with neither the volumes of NP-zones nor the total graft volume. The results suggest that P-zones in striatal grafts mediate graft-derived functional recovery in a complex task such as skilled forelimb use. Although the antioxidant treatment with α-phenyl-tert-butyl nitrone failed to promote graft survival, the positive correlation between the yield of DARPP-32-positive cells in the graft and the extent of the functional recovery highly warrants further attempts to increase the yield of the striatal component in the graft.
影响因子：
3.2
作者：
HEDREEN, JC;BACON, SJ;PRICE, DL
通讯作者：
PRICE, DL