title: Apoptosis and impaired axonal regeneration of sensory neurons after nerve crush in diabetic rats.
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.
authors.affiliation: Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kogawa
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: M
authors.initials: M
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: R
authors.initials: R
authors.lastname: Kikkawa
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002352:Carrier Proteins; D016755:Proto-Oncogene Proteins c-jun; D014665:Vasodilator Agents; C025090:ONO 1206; D000242:Cyclic AMP; D000527:Alprostadil