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5-Bromo-2'-deoxyuridine Is Selectively Toxic to Neuronal Precursors in Vitro

5-Bromo-2'-deoxyuridine Is Selectively Toxic to Neuronal Precursors in Vitro

Maeve A Caldwell, Xiaoling He, Clive N Svendsen

Eur J Neurosci. 2005 Dec;22(11):2965-70.

PMID: 16324131

Abstract:

The effect of 5-bromo-2'-deoxyuridine (BrdU) incorporation on the phenotype of progeny derived from expanded E18 rat striatal precursors was examined. BrdU was administered to cultures for 24 h prior to differentiation. Results revealed that there was selective toxicity of this compound to developing TuJ1+ neurons, but not glia, at concentrations used in most labelling studies. Therefore, a BrdU dose-response curve from 0.2 microM to 10 microM was established. The optimum dose of BrdU for labelling cells was 0.2 microM, well below the 1-10 microm recommended concentration. This dose resulted in the survival of significantly more newborn BrdU/TuJ1+ double-labelled neurons and eliminated the toxic effects of BrdU. Administration of 10 microm BrdU resulted in a significant decrease in extracellular regulated kinase (ERK) phosphorylation compared with untreated cultures, this could be completely restored by the administration of either N-methyl-D-aspartate (NMDA) receptor antagonists such as MK801 or the nitric oxide synthesis inhibitor L-methyl-arginine methyl ester (L-NAME). Our results show that high levels of BrdU are selectively toxic to neurons through a mechanism that activates classical cell death pathways. This has implications for labelling studies both in vivo and in vitro.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP59143	5-Bromo-2′-deoxyuridine		59-14-3	Price

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