Increased cyclic AMP in in vitro regenerating frog sciatic nerves inhibits Schwann cell proliferation but has no effect on axonal outgrowth.

Abstract

In the present study the role of cAMP for axonal outgrowth and Schwann cell proliferation was studied using the cultured frog sciatic nerve. An intrinsic rise in nerve and ganglionic cAMP could be measured as a response to nerve injury, both in vitro and in vivo. Treatment with 0.1-1.0 microM forskolin, an activator of the cAMP-generating enzyme adenylyl cyclase, increased the cAMP content up to 13-fold, but was yet without effect on axonal outgrowth during an 8-day culturing period. HA-1004, an inhibitor of cAMP-dependent protein kinase, also lacked effect on the regeneration. In contrast, the proliferation of Schwann cells, measured as [3H]thymidine incorporation, was inhibited to about 70% of control by forskolin, whereas HA-1004 stimulated proliferation to approximately 130% of control. The results suggest that cAMP is involved in the injury-induced proliferation of Schwann cells of an adult peripheral nerve but that it lacks a central role in the regeneration of sensory axons of such nerves.