The Regulatory Mechanism of Neurogenesis by IGF-1 in Adult Mice

Abstract

Growth factors like insulin-like growth factor 1 (IGF-1) is reported to mediate neurogenesis in the subgranular zone (SGZ) and the subventricular zone (SVZ) of the adult mammalian brain, but its regulatory mechanism remains unclear. We generated transgenic mice overexpressing IGF-1 specifically in neural stem cells (NSCs) and assessed the effect of IGF-1 on neurogenesis in adult mice NSCs. Overexpression of IGF-1 could stimulate the expression of phospho-Akt and phospho-ERK1/2 while inducing proliferation and differentiation of NSCs in the SGZ and SVZ. The MEK/ERK inhibitor U0126 could inhibit ERK1/2 phosphorylation, further inhibiting the proliferation of NSCs in the SGZ and SVZ but had no effect on the phosphorylation of Akt. By contrast, The PI3K/Akt inhibitor LY294002 inhibited phosphorylation of Akt and differentiation of NSCs in the SGZ and SVZ, resulting in no change in the proliferation of NSCs and ERK1/2 phosphorylation. These results demonstrate that IGF-1 upregulates the proliferation of NSCs by triggering MEK/ERK pathway signaling in the adult mice SGZ and SVZ. Meanwhile, IGF-1 also induces differentiation of NSCs via the PI3K/Akt pathway in adult mice. However, we found no evidence of crosstalk between the PI3K/Akt and MEK/ERK pathways in adult mice NSCs. Our work provides new experimental evidence of the involvement of the PI3K/Akt and MEK/ERK pathways in the proliferation and differentiation of the NSCs of adult mice.

Brain Insulin-Like Growth Factor-I Directs the Transition from Stem Cells to Mature Neurons During Postnatal/Adult Hippocampal Neurogenesis

“…The increase in the number of cycling cells detected in the Igf‐I KO mouse seems not to agree with previous data from studies into the action of exogenous IGF‐I. Indeed, IGF‐I stimulates the proliferation of embryonic NSCs and the overexpression or peripheral administration of IGF‐I enhances the number of proliferative cells in the postnatal/adult HP . By contrast and in line with our results, more proliferative cells in the postnatal SGZ of global Igf‐I KO mice were previously reported .…”

“…Conditional deletion of the Igf‐I receptor gene ( Igf‐IR ) using the Nestin‐Cre strategy produces almost complete loss of the DG in mice . Moreover, exogenous IGF‐I promotes the proliferation of progenitor cells in the adult HP, both in culture and in vivo . This enhancement in cell proliferation is followed by the formation of granule neurons .…”

Adult neurogenesis and neurodegenerative diseases: A systems biology perspective

“…IGF-1 induces the proliferation and differentiation of NSCs via MEK/ERK pathway signaling and the PI3K/Akt pathway signaling in the SGZ and SVZ, respectively [Yuan et al, 2015]. …”

Enhancement of neural stem cell survival, proliferation and differentiation by IGF-1 delivery in graphene oxide-incorporated PLGA electrospun nanofibrous mats

“…12,13 A previous study has shown that IGF-1 promotes the proliferation of NSCs by interacting with the insulin-like growth factor 1 receptor (IGF-1R), which may activate the PI3K/AKT and MAP kinase pathways. 14 The IGF/IGFR system regulates the differentiation of neurons, astrocytes, and oligodendrocytes generated from NSCs in embryonic and adult brains. 15,16 In addition, IGF is also involved in the regulation of NSC migration, which is mediated by the activation of the PI3K pathway and by phosphorylation of the reelin signal transducer.…”