Transforming growth factor-beta1 is a negative modulator of adult neurogenesis

J Neuropathol Exp Neurol. 2006 Apr;65(4):358-70. doi: 10.1097/01.jnen.0000218444.53405.f0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1