The effect of IGF-1 on hippocampal neurogenesis is known to rely on the activation of diverse intracellular regulatory cascades, including ERK and PI3K, following IGF-1 binding to IGF-1R [34]. Besides, overexpression of IGF-1 in aged mice also significantly increased the phosphorylation level ofCa2+- calmodulin-dependent kinase II (CaMKII) [26], a downstream protein of PLCγ pathway [12]. Taken together these studies indicate that IGF-1 exerts regulatory control over hippocampal neurogenesis sharing similar signals (PLCγ, PI3K and ERK) with BDNF pathways (Figure 1).