POLYAMINES PROMOTE REGENERATION OF INJURED AXONS OF CULTURED RAT HIPPOCAMPAL-NEURONS

Axons of cultured rat hippocampal neurons were injured by local irradiation of laser beam, and the effects of spermine, spermidine and putrescine on neurite regeneration following axonal injury were investigated. The axonal growth was stopped by laser irradiation, but addition of spermine remarkably promoted the axonal re-elongation from the injured site. Spermine affected neither the neurite branching at proximal part of injured axons nor the growth of uninjured dendrites. The effect of spermine was concentration dependent and seen maximally at a concentration of 10(-8) M. Spermidine and putrescine also promoted the axonal re-elongation in a concentration-dependent manner. The effects of three polyamines were very similar, and no additivity was observed when maximally effective concentrations of polyamines were added together, suggesting that they act through a common mechanism. Unlike polyamines, basic fibroblast growth factor (bFGF) did not promote the axonal re-elongation from the injured site, but rather stimulated the formation of axonal branches at proximal part of injured axons, supporting that the promotion of axonal re-elongation is a specific action of polyamines. Concomitant addition of spermine and bFGF additively or synergistically promoted both the axonal re-elongation from the injured site and the branch formation at proximal part of injured axons. These data suggest that polyamines have a capability of promoting axonal regeneration of brain neurons after lesioning.