Apoptosis and impaired axonal regeneration of sensory neurons after nerve crush in diabetic rats

We investigated the possible induction of apoptosis of dorsal root ganglion (DRG) neurons and the defect of nerve regeneration after crush injury with reference to the JNK/c-jun and cAMP pathway in streptozocin-induced diabet ic rats. In addition, the effects of a PGE(1) analogue were tested in diabe tic rats. At day 0 (before axonal injury), no TUNEL-positive DRG neurons we re observed in any group. From day 1 to 7 after axonal injury, TUNEL-positi ve DRG neurons were seen in diabetic rats, but not in non-diabetic or PGE(1 )-treated diabetic rats. The regeneration distance at day 7 after crush inj ury was shorter in diabetic rats than in the other groups of rats. The time course of JNK/c-jun phosphorylation did not parallel apoptosis. At day 7, the cAMP content of DRG was higher than that at day 0 in non-diabetic and P GE(1)-treated rats, whereas it was not increased after 7 days in diabetic r ats. These results indicate that in diabetic rats apoptosis of DRG neurons is induced by axonal injury independently of the JNK/c-jun and cAMP pathway and that PGE(1) rescues DRG neurons from apoptosis and improves axonal reg eneration in diabetic rats. NeuroReport 11:663-667 (C) 2000 Lippincott Will iams & Wilkins.