Schneider J S, Rothblat D S, DiStefano L
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
Brain Res. 1994 Apr 18;643(1-2):86-91. doi: 10.1016/0006-8993(94)90012-4.
Administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to cats results in a parkinsonian syndrome that spontaneously recovers by 6 weeks after induction. Striatal dopamine depletions in these animals are heterogenous with more extensive damage dorsolaterally than ventromedially. Measures of extracellular dopamine levels by in vivo microdialysis showed that dopamine released from a relatively preserved ventral striatal innervation can diffuse over a distance of 5.5 mm to 7.0 mm to the more extensively denervated dorsolateral striatum, where it may influence sensorimotor activities and contribute to functional recovery. Diffusion of dopamine through a large volume of striatal tissue was observed in cats 6 weeks after an MPTP-induced lesion and in normal cats with pharmacologically induced dopamine reuptake inhibition, but not in normal animals without reuptake inhibition. In cats recovered from MPTP-induced parkinsonism, a greater amount of dopamine was recovered from the extracellular fluid in the dorsolateral caudate following stimulated release of dopamine from the ventromedial striatum than after stimulated release locally in the dorsolateral caudate. These results suggest volume transmission of dopamine over large distances is possible and perhaps an important contributor to functional recovery from a large dopamine-depleting lesion. These results may also form the basis for understanding how limited reinnervation of the striatum by grafts or trophic factor therapies may lead to significant functional improvement.
给猫注射神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）会导致帕金森综合征，诱导后6周可自发恢复。这些动物的纹状体多巴胺耗竭是异质性的，背外侧比腹内侧损伤更广泛。通过体内微透析测量细胞外多巴胺水平表明，从相对保留的腹侧纹状体神经支配释放的多巴胺可以扩散5.5毫米至7.0毫米的距离，到达去神经支配更广泛的背外侧纹状体，在那里它可能影响感觉运动活动并有助于功能恢复。在MPTP诱导损伤6周后的猫和药理诱导多巴胺再摄取抑制的正常猫中观察到多巴胺通过大量纹状体组织的扩散，但在没有再摄取抑制的正常动物中未观察到。在从MPTP诱导的帕金森病中恢复的猫中，与在背外侧尾状核局部刺激释放多巴胺后相比，在腹内侧纹状体刺激释放多巴胺后，背外侧尾状核细胞外液中回收的多巴胺量更多。这些结果表明多巴胺远距离的容积传递是可能的，并且可能是从大量多巴胺耗竭性损伤中功能恢复的重要因素。这些结果也可能为理解移植物或神经营养因子疗法对纹状体的有限再支配如何导致显著的功能改善奠定基础。
