Peripheral infusion of IGF-I selectively induces neurogenesis in the adultrat hippocampus

In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic val ue as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have n eurotrophic properties. The relationship between IGF-I and adult hippocampa l neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular prolifera tion in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of p rogenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate i n progenitor progeny, we characterized the colocalization of BrdU-immunolab eled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuron al markers Calbindin D-28K, microtubule-associated protein-2, and NeuN. The re was no difference in the fraction of newly generated astrocytes. Thus, o ur results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17% (p < 0.001) incr ease in the number of new neurons in IGF-I-treated animals compared with co ntrols.