Circulating Insulin-like Growth Factor I Regulates Its Receptor in the Brain of Male Mice

Abstract

The role of insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) in brain pathology is still unclear. Thus, either reduction of IGF-IR or treatment with IGF-I, two apparently opposite actions, has proven beneficial in brain diseases such as Alzheimer´s dementia (AD). A possible explanation of this discrepancy is that IGF-I down-regulates brain IGF-IR levels, as previously seen in a mouse AD model. We now explored whether under normal conditions IGF-I modulates its receptor. We first observed that in vitro, IGF-I reduced IGF-IR mRNA levels in all types of brain cells including neurons, astrocytes, microglia, endothelial cells, and oligodendrocytes. IGF-I also inhibited its own expression in neurons and brain endothelium. Next, we analyzed in vivo actions of IGF-I. As serum IGF-I can enter the brain, we injected mice with IGF-I intraperitoneously. As soon as one hour after injection, decreased hippocampal IGF-I levels were observed, followed by increased IGF-I and IGF-IR mRNAs six hours later. As ...