Embryonic Substantia Nigra Grafts Show Directional Outgrowth to Cografted Striatal Grafts and Potential for Pathway Reconstruction in Nonhuman Primate
Embryonic Substantia Nigra Grafts Show Directional Outgrowth to Cografted Striatal Grafts and Potential for Pathway Reconstruction in Nonhuman Primate
复制标题
胚胎黑质移植物显示出向共移植纹状体移植物的定向生长以及非人类灵长类动物通路重建的潜力
DOI：
10.3727/096368908784423274
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发表时间：
2008
影响因子：
3.3
通讯作者：
D. Redmond
中科院分区：
文献类型：
--
作者：
J. Sladek;K. Bjugstad;T. Collier;E. Bundock;B. Blanchard;J. Elsworth;R. Roth;D. Redmond
胚胎多巴胺（DA）神经元移植已被测试为治疗帕金森病的一种方法。大多数研究将DA神经元置于纹状体而不是黑质（SN）中。重建这条DA通路可以为移植物神经元控制DA释放建立一个更有利的环境。为了验证这一点，我们使用纹状体共移植物来刺激非洲绿猴胚胎SN的DA轴突生长，该胚胎SN与宿主SN相邻植入。胚胎纹状体植入于吻侧至颈侧的三个渐进距离之一。免疫组织化学分析显示，在移植后12-36周，SN移植的DA神经元存活并有神经炎生长。每只动物均有大量DA神经元存活。大部分从SN移植物中流出的纤维向体表方向运动。纹状体移植物显示出目标导向生长的证据，并且含有密集的DA轴突，可以追溯到它们在SN移植物中的起源。从移植物中伸出的DA神经突存在极性；也就是说，那些在移植物尾端看到的似乎没有组织成定向流出，而那些在吻侧排列成线性轮廓，流向纹状体移植物。一些到达纹状体移植物的TH纤维似乎来自于SN的残留DA神经元。这些发现表明，移植的DA神经元可以通过脑干和猴脑尾间脑将神经突延伸到所需的目标数毫米，这有利于将移植的神经元置于其神经回路的适当位置进行电路重建。进一步的研究将评估这种方法在神经移植后用于恢复非人灵长类动物运动平衡的程度。
Transplantation of embryonic dopamine (DA) neurons has been tested as a therapy for Parkinson's disease. Most studies placed DA neurons into the striatum instead of the substantia nigra (SN). Reconstruction of this DA pathway could serve to establish a more favorable environment for control of DA release by grafted neurons. To test this we used cografts of striatum to stimulate growth of DA axons from embryonic SN that was implanted adjacent to the host SN in African green monkeys. Embryonic striatum was implanted at one of three progressive distances rostral to the SN. Immunohistochemical analysis revealed DA neuron survival and neuritic outgrowth from the SN grafts at 12–36 weeks after grafting. Each animal showed survival of substantial numbers of DA neurons. Most fibers that exited SN grafts coursed rostrally. Striatal grafts showed evidence of target-directed outgrowth and contained dense patterns of DA axons that could be traced from their origin in the SN grafts. A polarity existed for DA neurites that exited the grafts; that is, those seen caudal to the grafts did not appear to be organized into a directional outflow while those on the rostral side were arranged in linear profiles coursing toward the striatal grafts. Some TH fibers that reached the striatal grafts appeared to arise from the residual DA neurons of the SN. These findings suggest that grafted DA neurons can extend neurites toward a desired target over several millimeters through the brain stem and caudal diencephalon of the monkey brain, which favors the prospect of circuit reconstruction from grafted neurons placed into appropriate locations in their neural circuitry. Further study will assess the degree to which this approach can be used to restore motor balance in the nonhuman primate following neural transplantation.
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DOI：
10.1016/0165-3806(82)90095-5
发表时间：
1982-01-01
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
LEVITT, P;RAKIC, P
通讯作者：
RAKIC, P
来自多个供体的纹状体内移植物不会导致非人灵长类动物中多巴胺神经元的存活率成比例增加。
影响因子：
3.3
作者：
SladekJr,JR;Collier,TJ;Elsworth,JD;Roth,RH;Taylor,JR;RedmondJr,DE
通讯作者：
RedmondJr,DE
胎儿多巴胺神经移植物：对甲基苯基四氢吡啶诱导的猴子帕金森病的长期逆转。
影响因子：
--
作者：
SladekJr,JR;RedmondJr,DE;Collier,TJ;Blount,JP;Elsworth,JD;Taylor,JR;Roth,RH
通讯作者：
Roth,RH
假手术并不能改善 MPTP 引起的猴子行为缺陷。
影响因子：
3.3
作者：
Taylor,JR;Elsworth,JD;SladekJr,JR;Collier,TJ;Roth,RH;RedmondJr,DE
通讯作者：
RedmondJr,DE
体外胚胎中脑多巴胺神经元的目标神经元特异性过程形成。
DOI：
10.1073/pnas.78.2.1264
发表时间：
1981
影响因子：
11.1
作者：
Hemmendinger,LM;Garber,BB;Hoffmann,PC;Heller,A
通讯作者：
Heller,A