Antagonistic effect of N-(3-Aminopropyl)cyclohexylamine on neurotrophic action of spermine in primary cultured rat hippocampal and cerebellar neurons

We previously found that spermine potently promotes the neuronal survival and regeneration of primary cultured brain neurons. N-(3-Aminopropyl)cyclohexylamine (APCHA) was originally developed as a spermine synthase inhibitor. To test if endogenous spermine biosynthesis contributes to neuronal survival and morphogenesis, we examined the effects of APCHA in primary cultured rat hippocampal and cerebellar neurons. APCHA at concentrations up to 10(-6) M did not affect the neuronal survival, but significantly blocked the survival-promoting effect of spermine (10(-8) M). APCHA also blocked the spermine-induced promotion of neurite regeneration following axotomy. Unlike APCHA, another cyclohexylamine derivative trans-4-methylcyclohexylamine did not affect the neurotrophic effect of spermine. These results suggest that in primary cultured brain neurons, APCHA works as a spermine antagonist rather than as a spermine synthesis inhibitor.