Expression of insulin‐like growth factor system genes during the early postnatal neurogenesis in the mouse hippocampus

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Abstract
Insulin‐like growth factor‐1 (IGF‐1) is essential to hippocampal neurogenesis and the neuronal response to hypoxia/ischemia injury. IGF (IGF‐1 and ‐2) signaling is mediated primarily by the type 1 IGF receptor (IGF‐1R) and modulated by six high‐affinity binding proteins (IGFBP) and the type 2 IGF receptor (IGF‐2R), collectively termed IGF system proteins. Defining the precise cells that express each is essential to understanding their roles. With the exception of IGFBP‐1, we found that mouse hippocampus expresses mRNA for each of these proteins during the first 2 weeks of postnatal life. Compared to postnatal day 14 (P14), mRNA abundance at P5 was higher for IGF‐1, IGFBP‐2, ‐3, and ‐5 (by 71%, 108%, 100%, and 98%, respectively), lower for IGF‐2, IGF‐2R, and IGFBP‐6 (by 65%, 78%, and 44%, respectively), and unchanged for IGF‐1R and IGFBP‐4. Using laser capture microdissection (LCM), we found that granule neurons and pyramidal neurons exhibited identical patterns of expression of IGF‐1, IGF‐1R, IGF‐2R, IGFBP‐2, and ‐4, but did not express other IGF system genes. We then compared IGF system expression in mature granule neurons and their progenitors. Progenitors exhibited higher mRNA levels of IGF‐1 and IGF‐1R (by 130% and 86%, respectively), lower levels of IGF‐2R (by 72%), and similar levels of IGFBP‐4. Our data support a role for IGF in hippocampal neurogenesis and provide evidence that IGF actions are regulated within a defined in vivo milieu.