Fig. 5. Mechanisms underlying the anti-mitotic and differentiating effects of CM_Cerebellum 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).