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

Neuroreport. 2000 Mar 20;11(4):663-7. doi: 10.1097/00001756-200003200-00003.

Abstract

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 diabetic rats. In addition, the effects of a PGE1 analogue were tested in diabetic rats. At day 0 (before axonal injury), no TUNEL-positive DRG neurons were observed in any group. From day 1 to 7 after axonal injury, TUNEL-positive DRG neurons were seen in diabetic rats, but not in non-diabetic or PGE1-treated diabetic rats. The regeneration distance at day 7 after crush injury 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 PGE1-treated rats, whereas it was not increased after 7 days in diabetic rats. 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 PGE1 rescues DRG neurons from apoptosis and improves axonal regeneration in diabetic rats.

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / pathology
  • Afferent Pathways / physiopathology*
  • Alprostadil / analogs & derivatives
  • Alprostadil / pharmacology
  • Alprostadil / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Axons / drug effects
  • Axons / metabolism
  • Axons / pathology*
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism
  • Cyclic AMP / analysis
  • Cyclic AMP / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / physiopathology*
  • Disease Models, Animal
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / physiopathology*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Nerve Crush*
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / analysis
  • Proto-Oncogene Proteins c-jun / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use

Substances

  • Carrier Proteins
  • Proto-Oncogene Proteins c-jun
  • Vasodilator Agents
  • ONO 1206
  • Cyclic AMP
  • Alprostadil