Morales Ingrid, Sanchez Alberto, Rodriguez-Sabate Clara, Rodriguez Manuel
Laboratory of Neurobiology and Experimental Neurology, Department of Physiology Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Laboratory of Neurobiology and Experimental Neurology, Department of Physiology Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain.
Behav Brain Res. 2015 Aug 1;289:19-28. doi: 10.1016/j.bbr.2015.04.019. Epub 2015 Apr 20.
Available evidence increasingly suggests that the degeneration of dopamine neurons in Parkinson's disease starts in the striatal axons and synaptic terminals. A selective procedure is described here to study the mechanisms involved in the striatal denervation of dopaminergic terminals. This procedure can also be used to analyze mechanisms involved in the dopaminergic re-innervation of the striatum, and the role of astrocytes and microglia in both processes. Adult Sprague-Dawley rats were injected in the lateral ventricles with increasing doses of 6-hydroxydopamine (12-50 μg), which generated a dose-dependent loss of dopaminergic synapses and axons in the striatum, followed by an axonal sprouting (weeks later) and by a progressive recovery of striatal dopaminergic synapses (months later). Both the degeneration and regeneration of the dopaminergic terminals were accompanied by astrogliosis. Because the experimental manipulations did not induce unspecific damage in the striatal tissue, this method could be particularly suitable to study the basic mechanisms involved in the distal degeneration and regeneration of dopaminergic nigrostriatal neurons, and the possible role of astrocytes and microglia in the dynamics of both processes.
现有证据越来越多地表明，帕金森病中多巴胺神经元的退化始于纹状体轴突和突触终末。本文描述了一种选择性程序，用于研究多巴胺能终末纹状体去神经支配所涉及的机制。该程序还可用于分析纹状体多巴胺能再支配所涉及的机制，以及星形胶质细胞和小胶质细胞在这两个过程中的作用。成年Sprague-Dawley大鼠侧脑室注射递增剂量的6-羟基多巴胺（12-50μg），这会导致纹状体中多巴胺能突触和轴突呈剂量依赖性丧失，随后出现轴突发芽（数周后）以及纹状体多巴胺能突触逐渐恢复（数月后）。多巴胺能终末的退化和再生均伴有星形胶质细胞增生。由于实验操作未在纹状体组织中引起非特异性损伤，因此该方法可能特别适合研究多巴胺能黑质纹状体神经元远端退化和再生所涉及的基本机制，以及星形胶质细胞和小胶质细胞在这两个过程动态变化中的可能作用。
