Transforming growth factor-beta1 is a negative modulator of adult neurogenesis.
Transforming growth factor (TGF)-beta1 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-beta1 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-beta1 in adult neural stem cell biology and neurogenesis. In adult neural stem and progenitor cell cultures and after intracerebroventricular infusion, TGF-beta1 induced a long-lasting inhibition of neural stem and progenitor cell proliferation and a reduction in neurogenesis. In vitro, although TGF-beta1 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-beta1 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-beta1 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-beta1-associated CNS diseases and pathologic conditions.
Wachs
Frank-Peter
FP
Department of Neurology, University of Regensburg, Regensburg, Germany.
Winner
Beate
B
Couillard-Despres
Sebastien
S
Schiller
Thorsten
T
Aigner
Robert
R
Winkler
Jürgen
J
Bogdahn
Ulrich
U
Aigner
Ludwig
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1