its translocation in PC12 cells [53], which indicates that the regulatory mechanism of BDNF on the activity of FoxO1 may not be associated with protein modification level. Our results also demonstrated that specific BDNF knockout can reduce FoxO1 expression, showing that BDNF can affect FoxO1 activity by gene transcription/translation regulation. However, the underlying mechanism seems to be complicated, as BDNF can activate multiple signaling pathways (PI3K/AKT, MEK/ERK, PLCγ-PKC and PLCγ-CaMKII, etc.) to regulate certain transcription factors (CREB and NF-κB, etc.) by inducing TrkB receptor phosphorylation [54], but the exact functional mechanism needs to be revealed in the future.
