title: Circulating Insulin-Like Growth Factor I Regulates Its Receptor in the Brain of Male Mice.
abstract: The role of IGF-1 and its receptor (IGF-1R) in brain pathology is still unclear. Thus, either reduction of IGF-IR or treatment with IGF-1, two apparently opposite actions, has proven beneficial in brain diseases such as Alzheimer's dementia. A possible explanation of this discrepancy is that IGF-1 down-regulates brain IGF-1R levels, as previously seen in a mouse Alzheimer's dementia model. We now explored whether under normal conditions IGF-1 modulates its receptor. We first observed that in vitro, IGF-1 reduced IGF-1R mRNA levels in all types of brain cells including neurons, astrocytes, microglia, endothelial cells, and oligodendrocytes. IGF-1 also inhibited its own expression in neurons and brain endothelium. Next, we analyzed the in vivo actions of IGF-1. Because serum IGF-1 can enter the brain, we injected mice with IGF-1 ip. As soon as 1 hour after the injection, decreased hippocampal IGF-1 levels were observed, followed by increased IGF-1 and IGF-1R mRNAs 6 hours later. Because environmental enrichment (EE) stimulates the entrance of serum IGF-1 into the brain, we analyzed whether a physiological entrance of IGF-1 also produced changes in brain IGF-1R. Stimulation of IGF-1R by EE triggered a gradual decrease in hippocampal IGF-1 levels. After 6 hours of EE exposure, IGF-1 levels reached a significant decrease in parallel with increased IGF-1R expression. After longer times, IGF-1R mRNA levels returned to baseline. Thus, under nonpathological conditions, IGF-1 regulates brain IGF-1R. Because baseline IGF-1R levels are rapidly restored, a tight control of brain IGF-1R expression seems to operate under physiological conditions.
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: A
authors: A
authors: Trueba-Saiz
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: A M
authors: AM
authors: Fernandez
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: T
authors: T
authors: Nishijima
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: M
authors: M
authors: Mecha
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: A
authors: A
authors: Santi
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: V
authors: V
authors: Munive
authors: Cajal Institute, CSIC, and Ciberned , Madrid, Spain.
authors: I Torres
authors: IT
authors: Aleman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1