PHOSPHOLIPASE-A2 ACTIVITY IS REQUIRED FOR REGENERATION OF SENSORY AXONS IN CULTURED ADULT SCIATIC-NERVES

The adult frog dorsal root ganglia (DRGs) and their sciatic nerves (Sc N) survive in organ culture for several days, About 3 days after a loc al test crush, the sensory axons start to regenerate into the distal n erve stump at a rate of approximately 0.6-0.9 mm/day, The axonal outgr owth is inhibited in a non-toxic way by low concentrations of three di fferent phospholipase A2 (PLA(2)) inhibitors: 4-bromophenacyl bromide (BPB), aristolochic acid, and oleyl-oxyethyl-phosphoryl-choline (OOPC) , In contrast, the outgrowth was slightly stimulated by 0.2 mu M melit tin, a PLA(2) activator, Most experiments refer to the effects of BPB, which was shown to almost completely inhibit outgrowth at a concentra tion which did not affect either ganglionic protein synthesis or axona l transport, Using a compartmental system it could clearly be shown th at BPB exerted its action in the outgrowth region, Other experiments s howed that the initial period (about 3 days), which precedes the outgr owth, was unaffected by BPB, Several structures, including axonal ones , showed immunoreactivity for the low molecular form of PLA(2) (sPLA(2 )). The results suggest that PLA(2) activity plays an important role i n nerve regeneration and exerts its action at a local level, where the growth cones move forward. (C) 1996 Wiley-Liss, Inc.