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Forschungsdatenbank PMU-SQQUID

Transforming growth factor-beta1 is a negative modulator of adult neurogenesis.
Wachs, FP; Winner, B; Couillard-Despres, S; Schiller, T; Aigner, R; Winkler, J; Bogdahn, U; Aigner, L;
J Neuropathol Exp Neurol. 2006; 65(4):358-370
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Couillard-Després Sébastien

Abstract

Transforming growth factor (TGF)-beta 1 has multiple functions in the adult central nervous system (CNS). It modulates inflammatory responses in the CNS and controls proliferation of microglia and astrocytes. In the diseased brain, TGF-beta 1 expression is upregulated and, depending on the cellular context, its activity can be beneficial or detrimental regarding regeneration. We focus on the role of TGF-beta 1 in adult neural stem cell biology and neurogenesis. In adult neural stem and progenitor cell cultures and after intracerebroventricular infusion, TGF-beta 1 induced a long-lasting inhibition of neural stem and progenitor cell proliferation and a reduction in neurogenesis. In vitro, although TGF-beta 1 specifically arrested neural stem and progenitor cells in the G0/1 phase of the cell cycle, it did not affect the self-renewal capacity and the differentiation fate of these cells. Also, in vivo, TGF-beta 1 did not influence the differentiation fate of newly generated cells as shown by bromo-deoxyuridine incorporation experiments. Based on these data, we suggest that TGF-beta 1 is an important signaling molecule involved in the control of neural stem and progenitor cell proliferation in the CNS. This might have potential implications for neurogenesis in a variety of TGF-beta 1-associated CNS diseases and pathologic conditions.


Useful keywords (using NLM MeSH Indexing)

Animals

Apoptosis/drug effects

Apoptosis/physiology

Blotting, Western

Brain/cytology*

Brain/drug effects

Brain/metabolism*

Cell Cycle/drug effects

Cell Cycle/physiology

Cell Differentiation/drug effects

Cell Differentiation/physiology

Cell Proliferation/drug effects

Female

Flow Cytometry

In Situ Nick-End Labeling

Neurons/drug effects*

Neurons/metabolism

Rats

Rats, Inbred F344

Reverse Transcriptase Polymerase Chain Reaction

Stem Cells/drug effects*

Stem Cells/metabolism

Transforming Growth Factor beta/metabolism

Transforming Growth Factor beta/pharmacology*

Transforming Growth Factor beta1


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