Abstract
The cytokine TWEAK is expressed in the brain and is induced in cerebral ischemia and other brain disorders. TWEAK regulates proliferation and differentiation of progenitor cells but its effect on adult neural progenitor cells is still unknown. Therefore, we investigated the proliferation of neural progenitor cells from the subventricular zone of adult mice in response to TWEAK treatment. TWEAK inhibited proliferation of neural progenitor cells through its membrane receptor Fn14. The reduced proliferation was not due to cell death. By using a reporter assay we found that TWEAK activated the transcription factor NF-κB in adult neural progenitor cells. Blockade of NF-κB signaling reversed the inhibition of cell proliferation by TWEAK. In addition, TWEAK induced neuronal differentiation of neural progenitor cells and lowered the expression of hes1, a transcription factor that prevents neuronal differentiation. In adult mice deficient of the TWEAK receptor Fn14, neurogenesis was reduced in the subventricular zone. In conclusion, our data show that TWEAK regulates adult neurogenesis in the subventricular zone by binding to the membrane receptor Fn14 and activating NF-κB.
| Original language | English |
|---|---|
| Journal | Molecular and Cellular Neuroscience |
| Volume | 46 |
| Issue number | 1 |
| Pages (from-to) | 325-332 |
| Number of pages | 8 |
| ISSN | 1044-7431 |
| DOIs | |
| Publication status | Published - 01.01.2011 |
Funding
We thank Linda Burkly, Biogen Idec, for providing recombinant human TWEAK and Fn14 −/− mice as well as helpful comments on the manuscript and Anne Régnier-Vigouroux, Heidelberg, for providing primary microglia. The research leading to these results received funding from the European Union's Seventh Framework Program FP7/2007–2013 under grant agreements 201024 and 202213 (European Stroke Network). MNS is a member of the postdoc program of the Medical Faculty, University of Heidelberg. MS is a member of the Excellence Cluster CellNetworks at Heidelberg University.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
