THE EARLY INTRACELLULAR SIGNALING PATHWAY FOR THE INSULIN INSULIN-LIKE GROWTH-FACTOR RECEPTOR FAMILY IN THE MAMMALIAN CENTRAL-NERVOUS-SYSTEM/

Several studies support the idea that the polypeptides belonging to th e family of insulin and insulin-like growth factors (IGFs) play an imp ortant role in brain development and continue to be produced in discre te areas of the adult brain. ht numerous neuronal populations within t he olfactory bulb, the cerebral and cerebellar cortex, the hippocampus , some diencephalic and brainstem nuclei, the spinal cord and the reti na, specific insulin and IGF receptors, as well as crucial components of the intracellular receptor signaling pathway have been demonstrated . Thus, mature neurons are endowed with the cellular machinery to resp ond to insulin and EGF stimulation. Studies in vitro and in vivo, usin g normal and transgenic animals, have led to the hypothesis that, in t he adult brain, IGF-I not only acts as a trophic factor, but also as a neuromodulator of some higher brain functions, such as long-term pote ntiation and depression. Furthermore, a trophic effect on certain neur onal populations becomes clearly evident in the ischemic brain or neur odegenerative disorders. Thus, the analysis of the early intracellular signaling pathway for the insulin/IGF receptor family in the brain is providing us with new intriguing findings on the way the mammalian br ain is sculpted and operates.