Insulin-like growth factor 1-induced alterations in lumbospinal monoamine dynamics

A wealth of evidence indicates that insulin-like growth factor (IGF-1) is i nvolved in neurotransmitter release, synaptic plasticity, morphogenesis and regulation of gene expression. RT-PCR and immunocytochemical-based techniq ues revealed that IGF-I and its receptor are highly expressed by different neuronal elements of the spinal cord lumbar enlargement. Accordingly, the p resent study intended to examine lumbospinal monoamine dynamics in the cont ext of the neurotrophic factor IGF-1. Spinal release of norepinephrine (NE) represented by 3-methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was enhance d by IGF-1. This action of IGF-1 was associated with a similar increase in both tyrosine hydroxylase (TH) immunoreactivity and the level of its mRNA, In contrast, neuronal contents of serotonin and its metabolite 5-hydroxyind oleacetic acid in IGF-1-treated animals remained at control level. Genistei n, a tyrosine kinase inhibitor, which by itself had no effect on NE metabol ism, abolished the induction effect of IGF-1 on TH and MHPG/NE ratio. Our r esults suggest that IGF-1 augments the lumbospinal noradrenergic system by an intracellular mechanism involving a receptor-linked tyrosine kinase. The physiological consequences of the IGF-1 actions are discussed in terms of neuroprotection and nociception.