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The cell cycle–apoptosis connection revisited in the adult brain

Bauer, Sylvian and Patterson, Paul H. (2005) The cell cycle–apoptosis connection revisited in the adult brain. Journal of Cell Biology, 171 (4). pp. 641-650. ISSN 0021-9525. http://resolver.caltech.edu/CaltechAUTHORS:BAUjcb05

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Abstract

Adult neurogenesis is studied in vivo using thymidine analogues such as bromodeoxyuridine (BrdU) to label DNA synthesis during the S phase of the cell cycle. However, BrdU may also label DNA synthesis events not directly related to cell proliferation, such as DNA repair and/or abortive reentry into the cell cycle, which can occur as part of an apoptotic process in postmitotic neurons. In this study, we used three well-characterized models of injury-induced neuronal apoptosis and the combined visualization of cell birth (BrdU labeling) and death (Tdt-mediated dUTP-biotin nick end labeling) to investigate the specificity of BrdU incorporation in the adult mouse brain in vivo. We present evidence that BrdU is not significantly incorporated during DNA repair and that labeling is not detected in vulnerable or dying postmitotic neurons, even when a high dose of BrdU is directly infused into the brain. These findings have important implications for a controversy surrounding adult neurogenesis: the connection between cell cycle reactivation and apoptosis of terminally differentiated neurons.


Item Type:Article
Additional Information:© 2005 The Rockefeller University Press. Submitted: 12 May 2005; accepted: 14 October 2005. We are grateful to D. McDowell for excellent assistance and to C. Pagtakhan for the gift of the rabbit monoclonal anti–cyclin D1 antibody. This study was supported by a fellowship from the John Douglas French Alzheimer’s Foundation to S. Bauer and a grant from the National Institute of Neurological Disorders and Stroke (5RO1NS45744) to P.H. Patterson.
Record Number:CaltechAUTHORS:BAUjcb05
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:BAUjcb05
Alternative URL:http://dx.doi.org/10.1083/jcb.200505072
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5247
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:06 Oct 2006
Last Modified:26 Dec 2012 09:04

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