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Forschungsdatenbank PMU-SQQUID

The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival.
Lehner, B; Sandner, B; Marschallinger, J; Lehner, C; Furtner, T; Couillard-Despres, S; Rivera, FJ; Brockhoff, G; Bauer, HC; Weidner, N; Aigner, L;
Cell Tissue Res. 2011; 345(3):313-328
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Bauer Hans Christian
Couillard-Després Sébastien
Furtner Tanja
Lehner Christine
Marschallinger Julia
Rivera Gomez-Barris Francisco J.

Abstract

5-Bromo-2"-deoxyuridin (BrdU) is frequently used in anaylsis of neural stem cell biology, in particular to label and to fate-map dividing cells. However, up to now, only a few studies have addressed the question as to whether BrdU labeling per se affects the cells to be investigated. Here, we focused on the potential impact of BrdU on neurosphere cultures derived from the adult rat brain and on proliferation of progenitors in vivo. In vitro, neurospheres were pulsed for 48 h with BrdU, and cell proliferation, cell cycle, differentiation, survival and adhesion properties were subsequently analyzed. BrdU inhibited the expansion of neural progenitors as assessed by MTS assay and increased the fraction of cells in the G0/G1-phase of the cell cycle. Moreover, BrdU increased cell death and dose-dependently induced adherence of NPCs. Cell adherence was accompanied by a reduced amount of active matrix-metalloproteinase-2 (MMP-2). Furthermore, BrdU repressed neuronal and oligodendroglial differentiation, whereas astroglial fate was not affected. In contrast to the in vitro situation, BrdU apparently did not influence endogenous proliferation of NPCs or neurogenesis in concentrations that are typically used for labeling of neural progenitors in vivo. Our results reveal so far uncharacterized effects of BrdU on adult NPCs. We conclude that, because of its ubiquitous use in stem cell biology, any potential effect of BrdU of NPCs has to be scrutinized prior to interpretation of data.


Useful keywords (using NLM MeSH Indexing)

Animals

Bromodeoxyuridine/pharmacology*

Cell Adhesion/drug effects

Cell Aggregation/drug effects

Cell Cycle/drug effects*

Cell Death/drug effects

Cell Differentiation/drug effects*

Cell Proliferation/drug effects

Cell Survival/drug effects

Cells, Cultured

Female

Male

Matrix Metalloproteinase 2/metabolism

Neural Stem Cells/cytology*

Neural Stem Cells/drug effects*

Neural Stem Cells/enzymology

Neural Stem Cells/transplantation

Phenotype

Rats

Rats, Inbred F344

Staining and Labeling

Stem Cell Transplantation


Find related publications in this database (Keywords)

Neural progenitors
Neurogenesis
Cell culture
Cell labeling
Rat (Fischer 344)