QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 10, 2003, 23(36):11453-11460

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (35) Citing Articles via Google Scholar Google Scholar Articles by Chen, P. Articles by Lavin, M. F. Search for Related Content PubMed PubMed Citation Articles by Chen, P. Articles by Lavin, M. F.

 Previous Article  |  Next Article 

Cellular/Molecular
Oxidative Stress Is Responsible for Deficient Survival and Dendritogenesis in Purkinje Neurons from Ataxia-Telangiectasia Mutated Mutant Mice

Philip Chen,¹ Cheng Peng,¹ John Luff,¹ Kevin Spring,¹ Dianne Watters,² Steven Bottle,³ Shigeki Furuya,⁴ and Martin F. Lavin^1,5

¹The Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia, ²School of Biomolecular and Biomedical Sciences, Griffith University, Nathan Campus, Brisbane, Queensland 4111, Australia, ³School of Physical Sciences, Queensland University of Technology, Brisbane 4001, Australia, ⁴National Circuit Mechanisms Research Group, Brain Science Institute, RIKEN, Saitama, 351-0198, Japan, and ⁵Department of Surgery, University of Queensland, Royal Brisbane Hospital, Herston, Queensland 4029, Australia

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.

Key words: ataxia-telangiectasia; neurodegeneration; Purkinje neurons; oxidative stress; cell cultures; Atm mutant mice

---

Received July 9, 2003; revised September 30, 2003; accepted October 3, 2003.

This article has been cited by other articles:

				J. Kim and P. K. Y. Wong Oxidative Stress Is Linked to ERK1/2-p16 Signaling-mediated Growth Defect in ATM-deficient Astrocytes J. Biol. Chem., May 22, 2009; 284(21): 14396 - 14404. [Abstract] [Full Text] [PDF]

				M. F. Lavin, N. Gueven, S. Bottle, and R. A. Gatti Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia Br. Med. Bull., June 23, 2007; (2007) ldm012v1. [Abstract] [Full Text] [PDF]

				N. D. Fernandes, Y. Sun, and B. D. Price Activation of the Kinase Activity of ATM by Retinoic Acid Is Required for CREB-dependent Differentiation of Neuroblastoma Cells J. Biol. Chem., June 1, 2007; 282(22): 16577 - 16584. [Abstract] [Full Text] [PDF]

				Y. Jiang, V. L. Scofield, M. Yan, W. Qiang, N. Liu, A. J. Reid, W. S. Lynn, and P. K. Y. Wong Retrovirus-Induced Oxidative Stress with Neuroimmunodegeneration Is Suppressed by Antioxidant Treatment with a Refined Monosodium {alpha}-Luminol (Galavit) J. Virol., May 1, 2006; 80(9): 4557 - 4569. [Abstract] [Full Text] [PDF]

				S. Lu, K. C. Shen, Y. Wang, S.C. Brooks, and Y. A. Wang Impaired hepatocyte survival and liver regeneration in Atm-deficient mice Hum. Mol. Genet., October 15, 2005; 14(20): 3019 - 3025. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help