Endogenous IGF1 enhances cell survival in the postnatal dentate gyrus

The dentate gyrus is selectively reduced in size in the insulin-like growth factor 1 (IGF1) null mouse brain. The purpose of this study was to determi ne whether this defect is due to reduced granule cell numbers, and if so, t o determine whether altered cell proliferation, survival, or both contribut e to attenuation of dentate gyrus size. At postnatal day 10 (P10), granule cell numbers were not significantly different in IGF1 null and littermate w ildtype (WT) dentate gyri. The subgranular zone cell population, however, w as relatively increased, and the granule cell layer population relatively d ecreased in the IGF1 null dentate gyrus. By P50, total dentate cell numbers were decreased by 20% (P = 0.01) in the IGF1 null mouse, although IGF1 nul l subgranular zone progenitor cells remained relatively increased compared with WT (38%, P < 0.05). IGF1 null dentate cell proliferation, assessed by thymidine analogue incorporation, was actually increased at P10 (33%, P < 0 .05) and P50 (167%, P = 0.001). Dentate granule cell death, assessed by the appearance of pycnotic cells and DNA fragmentation, was also significantly increased in the IGF1 null dentate (61%, P < 0.05 and 101%, P = 0.03). The se data suggest that endogenous IGF1 serves an important role in dentate gr anule cell survival during the course of postnatal brain development. In ad dition, this work suggests the potential of a compensatory mechanism promot ing increased dentate cell proliferation in the face of impaired cell survi val during postnatal neurogenesis. Published 2001 Wiley-Liss, Inc.(dagger).