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

Hidemi Misawa, Kazuko Nakata, Junko Matsuura, Yasuhiro Moriwaki, Koichiro Kawashima, Takahiko Shimizu, Takuji Shirasawa, Ryosuke Takahashi

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalNeurobiology of Disease
Volume23
Issue number1
DOIs
Publication statusPublished - 2006 Jul

Fingerprint

Motor Neurons
Superoxides
Superoxide Dismutase
Axons
Neurons
Wounds and Injuries
Knockout Mice
Neurodegenerative Diseases
Transgenic Mice
Alleles
Parturition

Keywords

  • Amyotrophic lateral sclerosis
  • Conditional knockout
  • Mitochondria
  • Motor neurons
  • Nerve injury
  • Oxidative stress
  • SOD2

ASJC Scopus subject areas

  • Neurology

Cite this

Conditional knockout of Mn superoxide dismutase in postnatal motor neurons reveals resistance to mitochondrial generated superoxide radicals. / Misawa, Hidemi; Nakata, Kazuko; Matsuura, Junko; Moriwaki, Yasuhiro; Kawashima, Koichiro; Shimizu, Takahiko; Shirasawa, Takuji; Takahashi, Ryosuke.

In: Neurobiology of Disease, Vol. 23, No. 1, 07.2006, p. 169-177.

Research output: Contribution to journalArticle

Misawa, Hidemi ; Nakata, Kazuko ; Matsuura, Junko ; Moriwaki, Yasuhiro ; Kawashima, Koichiro ; Shimizu, Takahiko ; Shirasawa, Takuji ; Takahashi, Ryosuke. / Conditional knockout of Mn superoxide dismutase in postnatal motor neurons reveals resistance to mitochondrial generated superoxide radicals. In: Neurobiology of Disease. 2006 ; Vol. 23, No. 1. pp. 169-177.
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