Trophic Actions of IGF-I, IGF-II and Insulin on Cholinergic and Dopaminergic Brain Neurons

Abstract

Insulin, IGF-I and IGF-II have only recently been proposed to possess physiological functions distinctive for the central nervous system (review: Baskin et al., 1988). Receptors for insulin and the IGFs are found in rat brain and seem to be heterogeneously distributed (Hill et al., 1986; Mendelson, 1987; Bohannon et al., 1988). While evidence that insulin occurs in the brain is still equivocal (Baskin et al., 1988), mRNAs for IGF-I and IGF-II were detected in many brain areas and are differentially regulated during development (Rotwein et al., 1988). With cell culture methods it has been shown that insulin, IGF-I and IGF-II can have effects on neurons which are generally described as “neurotrophic”. Thus, in cultures of brain cells these hormones promote neuron survival, neurite extension, and expression of neuron-specific genes and, in astrocytes but possibly also in neurons, DNA synthesis (Bhat, 1983; Lenoir and Honegger, 1983; Mill et al., 1985; Recio-Pinto et al., 1986; Aizenman and de Vellis, 1987; Kyriakis et al., 1987; Avola et al., 1988; DiCicco-Bloom and Black, 1988). These effects are reminiscent of those produced by NGF in cell cultures. NGF and other polypeptide growth factors are believed to play decisive roles in the mammalian nervous system, particularly during early development but also in the adult organism (reviews: Thoenen et al., 1987; Snider and Johnson, 1989; Barde, 1989). Best established are the roles of NGF and brain-derived neurotrophic factor (BDNF) in the control of neuronal survival during development of certain peripheral neuron populations (Thoenen et al., 1987; Barde, 1989) and there is initial evidence for a similar action of neurotrophin-3, a polypeptide related to NGF and BDNF (Hohn et al., 1989; Maisonpierre et al., 1990).