Liang Chang-Lin, Wang Tom T, Luby-Phelps Kate, German Dwight C
Department of Psychiatry, University of Texas, Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75390-9070, USA.
Exp Neurol. 2007 Feb;203(2):370-80. doi: 10.1016/j.expneurol.2006.08.015. Epub 2006 Sep 28.
In Parkinson's disease (PD) there is a selective loss of certain midbrain dopaminergic (DA) neurons. The most vulnerable neurons reside in the substantia nigra zona compacta (SNC), whereas the DA neurons in the ventral tegmental area (VTA) and interfascicular (IF) nucleus are less vulnerable to degeneration. Many sporadic PD patients have a defect in mitochondria respiration, and some of the genes that cause PD are mitochondrial-related (e.g., PINK1, Parkin, DJ1). The present study sought to determine whether mitochondria mass is different in SNC neurons compared to other midbrain DA neurons and to non-DA neurons in the mouse. At the electron microscopic level, mitochondria in the SN DA neurons occupy 40% less of the soma and dendritic area than in the SN non-DA neurons. The area occupied by mitochondria in the SN DA neurons is also lower than in the VTA neurons, although not different from the IF neurons. The red nucleus somata have the largest percentage of the somata occupied by mitochondria (12%). Mitochondria size is related to somata size; the largest mitochondria are found in the red nucleus neurons and the smallest mitochondria are found in the IF neurons. At the light microscopic level, SNC, VTA and IF DA neurons have <50% of the cytoplasm immunostained with the mitochondrial antibody 1D6, whereas non-DA neurons in the same midbrain regions contain mitochondria areas up to >65% of the cytoplasm area. These data indicate that mitochondria size and mass are not the same for all neurons, and the SNC DA neurons have relatively low mitochondria mass. The low mitochondria mass in SNC DA neurons may contribute to the selective vulnerability of these neurons in certain rodent models of PD.
在帕金森病（PD）中，某些中脑多巴胺能（DA）神经元会选择性丧失。最易受损的神经元位于黑质致密部（SNC），而腹侧被盖区（VTA）和束间（IF）核中的DA神经元对变性的敏感性较低。许多散发性PD患者存在线粒体呼吸缺陷，并且一些导致PD的基因与线粒体相关（例如，PINK1、Parkin、DJ1）。本研究旨在确定与小鼠其他中脑DA神经元和非DA神经元相比，SNC神经元中的线粒体质量是否存在差异。在电子显微镜水平下，SN DA神经元中的线粒体在胞体和树突区域所占的比例比SN非DA神经元少40%。SN DA神经元中线粒体所占区域也低于VTA神经元，尽管与IF神经元无差异。红核胞体中线粒体所占胞体的百分比最大（12%）。线粒体大小与胞体大小相关；最大的线粒体见于红核神经元，最小的线粒体见于IF神经元。在光学显微镜水平下，SNC、VTA和IF DA神经元中用线粒体抗体1D6免疫染色的细胞质不到50%，而同一中脑区域的非DA神经元所含线粒体区域高达细胞质区域的65%以上。这些数据表明，并非所有神经元的线粒体大小和质量都相同，且SNC DA神经元的线粒体质量相对较低。SNC DA神经元中线粒体质量较低可能导致这些神经元在某些PD啮齿动物模型中具有选择性易损性。
