Oxidative Stress is Responsible for Deficient Survival and Dendritogenesis in Purkinje Neurons from Ataxia-Telangiectasia Mutated Mutant Mice

Philip Chen, Cheng Peng, John Luff, Kevin Spring, Dianne Watters, Steven Bottle, Shigeki Furuya, Martin F. Lavin

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Abstract

Atm gene-disrupted mice recapitulate the majority of characteristics observed in patients with the genetic disorder ataxia-telangiectasia (A-T). However, although they exhibit defects in neuromotor function and a distinct neurological phenotype, they do not show the progressive neurodegeneration seen in human patients, but there is evidence that ataxia-telangiectasia mutated (Atm)-deficient animals have elevated levels of oxidized macromolecules and some neuropathology. We report here that in vitro survival of cerebellar Purkinje cells from both Atm "knock-out" and Atm "knock-in" mice was significantly reduced compared with their wild-type littermates. Although most of the Purkinje neurons from wild-type mice exhibited extensive dendritic elongation and branching under these conditions, most neurons from Atm-deficient mice had dramatically reduced dendritic branching. An antioxidant (isoindoline nitroxide) prevented Purkinje cell death in Atm-deficient mice and enhanced dendritogenesis to wild-type levels. Furthermore, administration of the antioxidant throughout pregnancy had a small enhancing effect on Purkinje neuron survival in Atm gene-disrupted animals and protected against oxidative stress in older animals. These data provide strong evidence for a defect in the cerebellum of Atm-deficient mice and suggest that oxidative stress contributes to this phenotype.

Original languageEnglish
Pages (from-to)11453-11460
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number36
Publication statusPublished - Dec 10 2003
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Chen, P., Peng, C., Luff, J., Spring, K., Watters, D., Bottle, S., ... Lavin, M. F. (2003). Oxidative Stress is Responsible for Deficient Survival and Dendritogenesis in Purkinje Neurons from Ataxia-Telangiectasia Mutated Mutant Mice. Journal of Neuroscience, 23(36), 11453-11460.