Effect of insulin like-growth factor on development and survival of cholinergic neurons

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We investigated the effect of insulin-like growth factors II (IGFII) on septal primary cultures from mouse embryonic day 15 brains. The addition of IGFII to septal cultures enhanced total choline acetyltaransferase (ChAT) activity in a dose-dependent manner. The effect of IGFII on ChAT activity was completely blocked by anti-IGFII/M-6-P receptor antibodies, whereas the antisera alone had no effect on the enzyme activity. Double-labeled immunohistochemical studies revealed that most ChAT-positive neurons expressed IGFII/M-6-P receptor immunoreactivity. These results indicate that the trophic effect of IGFII results from the direct action of this molecule through the IGFII/M-6-P receptor in septal cholinergic neurons. We also examined expression and production of interleukin-3 (IL-3) mRNA and IL-3protein in mouse primary cultured neurons and glia by the reverse transcription and polymerase chain reaction and bioassay using an IL-3-dependent cell line. IL-3 mRNA was demonstrated mainly in hippocampal neurons but not in glia, while a small but definite production of bioactive IL-3 was detected in septal and hippocampal neuronal cultures. Thus, endogenous IL-3 might be produced by certain neurons in situ.