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PMID:16677818
| Citation |
Misawa, H, Nakata, K, Matsuura, J, Moriwaki, Y, Kawashima, K, Shimizu, T, Shirasawa, T and Takahashi, R (2006) Conditional knockout of Mn superoxide dismutase in postnatal motor neurons reveals resistance to mitochondrial generated superoxide radicals. Neurobiol. Dis. 23:169-77 |
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| Abstract |
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 pathological 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. |
| Links |
PubMed Online version:10.1016/j.nbd.2006.02.014 |
| Keywords |
Animals; Axotomy; Blotting, Western; Cell Survival; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Electron, Transmission; Mitochondria/metabolism; Motor Neurons/enzymology; Motor Neurons/pathology; Muscle, Skeletal/innervation; Muscle, Skeletal/pathology; Oxidative Stress/physiology; Superoxide Dismutase/deficiency; Superoxide Dismutase/genetics; Superoxides/metabolism; Wallerian Degeneration/metabolism; Wallerian Degeneration/pathology |
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Significance
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