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Published online 15 November 2005. doi:10.1083/jcb.200505072
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 171, Number 4, 641-650
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Article

 The cell cycle–apoptosis connection revisited in the adult brain

Sylvian Bauer and Paul H. Patterson

Biology Division, California Institute of Technology, Pasadena, CA 91125

Correspondence to Paul H. Patterson: php{at}caltech.edu

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.

Abbreviations used in this paper: AD, Alzheimer's disease; CA, cornu ammonis; casp-3, activated caspase 3; CldU, chlorodeoxyuridine; IdU, iododeoxyuridine; KA, kainic acid; OBX, olfactory bulbectomy; OE, olfactory epithelium; SGZ, subgranular zone; SVZ, subventricular zone.


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