Conditional knockout of Mn superoxide dismutase in postnatal motor neurons reveals resistance to mitochondrial generated superoxide radicals
Conditional knockout of Mn superoxide dismutase in postnatal motor neurons reveals resistance to mitochondrial generated superoxide radicals
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DOI：
10.1016/j.nbd.2006.02.014
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发表时间：
2006-07-01
影响因子：
6.1
通讯作者：
Takahashi, Ryosuke
中科院分区：
文献类型：
--
作者：
Misawa, Hidemi;Nakata, Kazuko;Takahashi, Ryosuke
线粒体功能障碍和氧化损伤与神经退行性疾病的发病机制有关。缺乏线粒体形式的超氧化物歧化酶（SOD 2）的小鼠在胚胎或出生后早期发育过程中死亡，排除了对成年组织中超氧化物的病理作用的分析。在这里，我们产生了出生后运动神经元特异性的SOD 2敲除杂交小鼠与floxed SOD 2等位基因VAChT-Cre转基因小鼠，其中Cre表达仅限于出生后的躯体运动神经元。SOD 2的免疫反应性，特别是失去了一个子集的somatomotor神经元，从而提高超氧化物的生产。然而，广泛的组织学检查显示，动物出生后1年内没有氧化损伤的迹象。然而，损伤后的远端神经轴突的解体加速在SOD 2缺陷的运动神经元。这些数据表明，出生后的运动神经元是令人惊讶的抗氧化损伤的神经源性超氧自由基，但这种损害可能会敏感轴突解体后神经损伤。(c)2006年爱思唯尔公司All rights reserved.
Mitochondrial dysfunction and oxidative damage are implicated in the pathogenesis of neurodegenerative disease. Mice deficient in the mitochondrial form of superoxide dismutase (SOD2) die during embryonic or early postnatal development, precluding analysis of a patho logical role for superoxide in adult tissue. Here, we generated postnatal motor neuron-specific SOD2 knockouts by crossing mice with floxed SOD2 alleles to VAChT-Cre transgenic mice in which Cre expression is restricted to postnatal somatomotor neurons. SOD2 immunoreactivity was specifically lost in a subset of somatomotor neurons resulting in enhanced superoxide production. Yet extensive histological examination revealed no signs of oxidative damage in animals up to 1 year after birth. However, disorganization of distal nerve axons following injury was accelerated in SOD2-deficient motor neurons. These data demonstrate that postnatal motor neurons are surprisingly resistant to oxidative damage from mitochondrial-derived superoxide radicals, but that such damage may sensitize axons to disorganization following nerve injury. (c) 2006 Elsevier Inc. All rights reserved.