Skip Navigation


Cerebral Cortex Advance Access originally published online on September 1, 2004
Cerebral Cortex 2005 15(6):696-707; doi:10.1093/cercor/bhh171
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
15/6/696    most recent
bhh171v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Narasimhaiah, R.
Right arrow Articles by Naegele, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Narasimhaiah, R.
Right arrow Articles by Naegele, J. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Cerebral Cortex V 15 N 6 © Oxford University Press 2004; all rights reserved

Oxidative Damage and Defective DNA Repair is Linked to Apoptosis of Migrating Neurons and Progenitors During Cerebral Cortex Development in Ku70-Deficient Mice

Roopashree Narasimhaiah1, Alexander Tuchman1, Stanley L. Lin1,2 and Janice R. Naegele1

1 Program in Neuroscience and Behavior, Department of Biology, Wesleyan University, Middletown, CT 06459-0171, USA and 2 Department of Psychiatry, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA

Address correspondence to Dr Janice R. Naegele, Department of Biology, Wesleyan University, Middletown, CT 06459-0170, USA. Email: jnaegele{at}wesleyan.edu.

DNA repair plays a critical, but imprecisely defined role in neuronal survival during cortical neurogenesis. We examined cortical development in mice deficient for the DNA end-joining protein, Ku70. At gestational day 14.5, corresponding to the peak of neurogenesis, the Ku70–/– embryonic cerebral cortex displayed 25- to 30-fold more cell death than heterozygous littermates, as judged by DNA breaks, pyknosis and active caspase-3. In Ku70–/– embryos only, large clusters of dying neurons were found in the intermediate zone. Cell death declined until P4, when the number of dying cells became comparable to that in heterozygous mice. Two groups of dying cells were evident: a GLAST+ neural progenitor population in the subventricular and ventricular zones, and a doublecortin+ immature neuron population in the intermediate zone, the latter exhibiting strong staining for oxidative DNA damage. Antioxidants and lower oxygen tension reduced the high levels of neuronal death in primary cortical cultures derived from Ku70–/– mice, but not the low levels of cell death in wildtype cortical cultures. Results indicate migrating cortical neurons undergo oxidative DNA damage, which is normally repaired by non-homologous end joining. Failure to repair oxidative damage triggers a form of apoptosis involving caspase-3 activation.

Key Words: apoptosis • immature neurons • Ku70 • NHEJ • oxidative damage • progenitors


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.