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- Title
5-Bromo-2′-deoxyuridine is selectively toxic to neuronal precursors in vitro.
- Authors
Caldwell, Maeve A.; He, Xiaoling; Svendsen, Clive N.
- 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 µ m to 10 µ m was established. The optimum dose of BrdU for labelling cells was 0.2 µ m, well below the 1–10 µm 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 µm 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.
- Subjects
NEURAL transmission; NEUROPLASTICITY; GENOTYPE-environment interaction; PHENOTYPES; PHYSIOLOGICAL adaptation; NEUROPHYSIOLOGY; GENETICS; NEURAL circuitry
- Publication
European Journal of Neuroscience, 2005, Vol 22, Issue 11, p2965
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2005.04504.x