Björklund A, Dunnett S B, Stenevi U, Lewis M E, Iversen S D
Brain Res. 1980 Oct 20;199(2):307-33. doi: 10.1016/0006-8993(80)90692-7.
Embryonic substantia nigra (SN) was transplanted to the neostriatum in adult rats subjected to a unilateral or serial bilateral destruction of the nigrostriatal dopamine (DA) pathway. The survival of the graft and the growth of DA-containing fibers from the graft into the host brain was studied by fluorescence histochemistry and micro-fluorometry. The motor asymmetry, and the contralateral 'sensory neglect' induced by a unilateral destruction of the nigrostriatal DA pathway, were monitored in the transplanted rats and in non-transplanted controls through repeated measurements of the amphetamine-and apomorphine-induced rotational behaviour, and through analysis of the rats performance in a number of sensorimotor tests. Finally, the development of aphagia and adipsia after a serial bilateral destruction of both nigrostriatal DA pathways were followed in rats bearing bilateral SN transplants and in lesioned non-transplanted controls. The results show that large parts of the dorsal neostriatum can be reinnervated by DA-containing axons from the intracortical transplant and that this new DA input can fully compensate for the amphetamine-induced motor assymmetry that resulted from the initial destruction of the innate nigrostriatal DA pathway. The fluorescence microscopical observations provide strong evidence that the compensation of the amphetamine-induced rotational response was specifically related to the re-establishment of a new DA input to the denervated neostriatum, and that the degree of rotational compensation was well correlated to the magnitude of ingrowth into the neostriatum. Subsequent surgical removal of the SN transplant reinstated the initial rotational behaviour. In sharp contrast to the marked compensation in motor asymmetry, the transplanted rats showed no tendency to recover in their sensorimotor performance. Thus, while the sensorimotor deficit had recovered in the control group a marked contralateral 'sensory neglect' remained in the transplanted animals. Furthermore, removal of the transplant produced a significant improvement in their sensorimotor performance within 3 days. In the bilaterally transplanted animals the presence of the transplants did not prevent the development of severe adipsia, aphagia and akinesia following the destruction of the remaining contralateral nigrostriatal pathway. In fact, the recovery from the consummatory deficits tended to be better in the lesioned control rats than in the transplanted ones. It is concluded that SN transplants reinnervation the dorsal part of the neostriatum are able to replace the innate SN in normalizing some aspects of the rats motor behaviour, while their sensorimotor deficits and deficits in consummatory behaviour were unaffected. It is suggested that this dissociation of transplant-induced recovery is due to the failure of the SN transplants to reinnervate those parts of the neostriatum which are most directly implicated in sensorimotor and consummatory behaviour.
将胚胎黑质移植到经单侧或连续双侧破坏黑质纹状体多巴胺（DA）通路的成年大鼠的新纹状体中。通过荧光组织化学和微量荧光测定法研究移植组织的存活情况以及从移植组织中长出的含DA纤维向宿主脑内的生长情况。通过反复测量苯丙胺和阿扑吗啡诱导的旋转行为，并分析大鼠在多项感觉运动测试中的表现，对移植大鼠和未移植对照大鼠中由单侧破坏黑质纹状体DA通路诱导的运动不对称以及对侧“感觉忽视”进行监测。最后，在双侧移植黑质的大鼠和损伤但未移植的对照大鼠中，追踪双侧黑质纹状体DA通路连续双侧破坏后出现的摄食和饮水障碍的发展情况。结果表明，来自脑内移植组织的含DA轴突可使背侧新纹状体的大部分区域重新获得神经支配，并且这种新的DA输入能够完全补偿因先天性黑质纹状体DA通路最初破坏而导致的苯丙胺诱导的运动不对称。荧光显微镜观察提供了有力证据，表明对苯丙胺诱导的旋转反应的补偿与向去神经支配的新纹状体重新建立新的DA输入密切相关，并且旋转补偿程度与长入新纹状体的程度密切相关。随后手术切除黑质移植组织可使最初的旋转行为恢复。与运动不对称方面的明显补偿形成鲜明对比的是，移植大鼠在感觉运动表现上没有恢复的趋势。因此，虽然对照组的感觉运动缺陷已经恢复，但移植动物中仍存在明显的对侧“感觉忽视”。此外，切除移植组织在3天内使其感觉运动表现有显著改善。在双侧移植的动物中；移植组织的存在并不能阻止在破坏剩余的对侧黑质纹状体通路后出现严重的饮水障碍、摄食障碍和运动不能。事实上，损伤对照大鼠在完成行为缺陷方面的恢复往往比移植大鼠更好。得出的结论是，黑质移植组织对新纹状体背侧部分的重新神经支配能够在使大鼠运动行为的某些方面恢复正常时替代先天性黑质，而它们的感觉运动缺陷和完成行为缺陷并未受到影响。有人提出，移植诱导的恢复出现这种分离现象是由于黑质移植组织未能使新纹状体中那些与感觉运动和完成行为最直接相关的部分重新获得神经支配。
