Conditional knockout of Mn superoxide dismutase in postnatal motor neurons reveals resistance to mitochondrial generated superoxide radicals

Neurobiology of Disease

Junko Matsuura¹  Kazuko Nakata²  Ryosuke Takahashi³  Yasuhiro Moriwaki⁴  Hidemi Misawa⁴  Koichiro Kawashima⁴  Takuji Shirasawa⁵  Takahiko Shimizu⁵ 

[1] Corresponding author. Department of Pharmacology, Kyoritsu University of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Fax. [phone].;Department of Pharmacology, Kyoritsu University of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan;Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2, Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan;Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, 2-6, Musashidai, Fuchu-shi, Tokyo 183-8526, Japan;Department of Pharmacology, Kyoritsu University of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan;

关键词: Motor neurons;    Oxidative stress;    Mitochondria;    Nerve injury;    Conditional knockout;    SOD2;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown