Reconstruction of the striato-nigro-striatal circuitry by simultaneous double dopaminergic grafts: a tracer study using fluorogold and horseradish peroxidase
Reconstruction of the striato-nigro-striatal circuitry by simultaneous double dopaminergic grafts: a tracer study using fluorogold and horseradish peroxidase
复制标题
DOI：
10.1016/s0006-8993(97)01055-x
复制
发表时间：
1997-12-05
期刊：
影响因子：
2.9
通讯作者：
Hong, M
中科院分区：
文献类型：
--
作者：
Mendez, I;Hong, M
神经移植治疗帕金森病（PD）的主要策略是在纹状体中异位放置多巴胺能移植物，以恢复宿主纹状体的多巴胺能神经支配。虽然在6-羟多巴胺损伤的PD啮齿动物模型中，纹状体内移植通常可以改善不对称旋转行为，但它们不太可能完全恢复多巴胺缺失引起的更复杂的感觉运动行为缺陷。重建黑质纹状体回路和黑质多巴胺能再神经化可能是促进多巴胺耗竭脑功能更完全恢复和提高多巴胺能移植临床疗效的必要条件。最近，我们证明了同时在纹状体内和神经内移植多巴胺能重建黑质纹状体通路[Mendez et al.， J. Neurosci. 16(1996) 7216-7227]。利用这一策略，我们发现将胚胎中脑腹侧组织移植物置于纹状体中，促进了中脑腹侧同种移植物轴突的生长和引导。由于发育中的组织明显具有促进轴突生长和沿黑质纹状体通路引导的能力，因此双移植策略可能有助于重建宿主-移植物连通性。目前的研究为纹状体-黑质纹状体环路的重建提供了证据，同时通过纹状体内和黑质内的多巴胺能移植。将逆行示踪剂氟金（FG）注射到纹状体中，在移植物内产生荧光标记的细胞。同样地，将FG注射到黑质中，在纹状体内和周围纹状体内产生荧光标记的细胞。注射顺行示踪剂辣根过氧化物酶（HRP）导致整个靶纹状体存在HRP反应产物。这些结果有力地支持了纹状体和纹状体在纹状体内和纹状体内同时移植多巴胺之间的联系的重建，并提示纹状体-黑质纹状体环路的重建。(C) 1997爱思唯尔科学有限公司
The main strategy in neural transplantation for Parkinson's disease (PD) has been the ectopic placement of dopaminergic grafts in the striatum in order to restore dopaminergic innervation to the host striatum. Although intrastriatal transplants usually improve asymmetric rotational behavior in the 6-hydroxydopamine lesioned rodent model of PD, they are less likely to completely restore the more complex sensorimotor behavioral deficits induced by dopamine loss. Re-establishment of the nigrostriatal circuitry and dopaminergic reinnervation of the substantia nigra may be necessary to promote a more complete restoration of function in the dopamine depleted brain and improve the clinical efficacy of dopaminergic transplants. Recently, we demonstrated the reconstruction of the nigrostriatal pathway by simultaneous intrastriatal and intranigral dopaminergic transplants [Mendez et al., J. Neurosci. 16 (1996) 7216-7227.]. Using this strategy, it was found that placing a graft of embryonic ventral mesencephalic tissue in the striatum promoted the growth and guidance of axons from a similar graft placed homotopically in the ventral mesencephalon. Since it is apparent that developing tissue has the ability to promote axonal growth and guidance along the nigrostriatal pathway, the double grafting strategy may contribute to re-establishing host-graft connectivity. The current study provides evidence of reconstruction of the striato-nigro-striatal loop circuitry by simultaneous intrastriatal and intranigral dopaminergic transplants. Injection of the retrograde tracer fluorogold (FG) into the striatum resulted in fluorescent labeled cells within the intranigral grafts. Similarly injection of FG into the nigra resulted in fluorescent labeled cells within the intrastriatal graft and surrounding striatum. Injection of the anterograde tracer horseradish peroxidase (HRP) resulted in the presence of HRP reaction product throughout the target striatum. These results strongly support the re-establishment of nigrostriatal and striatonigral connections between simultaneous intrastriatal and intranigral dopaminergic transplants and suggest reconstruction of the striato-nigro-striatal loop circuitry. (C) 1997 Elsevier Science B.V.