Enhancement of IGF-2-induced neurite outgrowth by IGF-binding protein-2 and osteoglycin in SH-SY5Y human neuroblastoma cells

A previous study using a mouse model of depression showed that chronic immobilization stress (CIS) reduces levels of insulin-like growth factor (IGF)-2, IGF binding protein 2 (IGFBP2), osteoglycin, and fibromodulin in the amygdala. Here, using human neuroblastoma cells, we tested whether these four proteins cooperatively modulate neuronal plasticity. We found that IGF-2 and IGFBP2 synergistically increased neurite outgrowth via enhanced early signaling through the IGF type 1 receptor. Furthermore, we found that osteoglycin, a small leucine-rich proteoglycan, significantly increased IGF-2/IGFPB2-induced neurite outgrowth, but fibromodulin had no effect. We also found that central amygdala neurons of CIS-induced depressive mouse showed a decreased total dendritic length. These findings suggest that CIS-responsive proteins modulate neuronal morphology during chronic stress.