Mitochondria mass is low in mouse substantia nigra dopamine neurons: Implications for Parkinson's disease

Mitochondria mass is low in mouse substantia nigra dopamine neurons: Implications for Parkinson's disease
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DOI:
10.1016/j.expneurol.2006.08.015
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发表时间:
2007-02-01
影响因子:
5.3
通讯作者:
German, Dwight C.
German, Dwight C.
中科院分区:
医学2区
文献类型:
--
作者:
Liang, Chang-Lin;Wang, Tom T.;German, Dwight C.

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在帕金森病(PD)中,存在某些中脑多巴胺能(DA)神经元的选择性损失。最脆弱的神经元位于黑质神经元(SNC),而腹侧被盖区(VTA)和束间核(IF)的DA神经元不太容易变性。许多散发性PD患者在线粒体呼吸中存在缺陷,并且导致PD的一些基因与肾脏相关(例如,PINK1,Parkin,DJ1)。本研究试图确定是否线粒体质量是不同的SNC神经元相比,其他中脑DA神经元和非DA神经元的小鼠。在电镜水平上,SN DA神经元的线粒体占索马和树突面积比SN non-DA神经元少40%。SN DA神经元中线粒体所占的面积也低于VTA神经元,尽管与IF神经元没有不同。线粒体在红核胞体中所占比例最大(12%)。线粒体大小与胞体大小有关;最大的线粒体存在于红核神经元中,最小的线粒体存在于IF神经元中。在光学显微镜水平,SNC、VTA和IF DA神经元具有< 50%的细胞质被线粒体抗体1D 6免疫染色,而在相同中脑区域中的非DA神经元含有高达细胞质面积的> 65%的线粒体面积。这些数据表明,线粒体的大小和质量是不相同的所有神经元,和SNC DA神经元具有相对较低的线粒体质量。SNC DA神经元中的低线粒体质量可能有助于这些神经元在某些啮齿动物模型中的PD的选择性脆弱性。(c)2006年爱思唯尔公司All rights reserved.
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. (c) 2006 Elsevier Inc. All rights reserved.