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Fig. 5. Mechanisms underlying the anti-mitotic and differentiating effects of
CMCerebellum and BDNF – possible opportunities for crosstalk
with TGFß signaling pathways. The anti-proliferative effects of BDNF
(measured by BrdU incorporation) are significantly attenuated in primary
hippocampal cells expressing a dominant-negative form of TGFß-RII. (B,C)
The MEK inhibitor PD98059 (0.1 µM) counteracts the anti-proliferative (B)
and pro-differentiating (C) effects of BDNF. (D) Transient transfection of
HiB5 cells with pBDNF results in increased TGFß2 reporter gene (3TP-Lux)
expression, an effect that is significantly attenuated by co-transfecting
dominant-negative forms (
) of either TRKB, TGFß-RII or SMAD4, or
by pretreatment with PD98059. (E) BDNF dose-dependently increases TGFß2
protein content in primary hippocampal cells; numerical data refer to
mean±s.d. (n=4-6) *P<0.05, **P<0.01,
***P<0.001 (versus appropriate controls).
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