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 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.
Kogawa
S
S
Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.
Yasuda
H
H
Terada
M
M
Maeda
K
K
Kikkawa
R
R
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
D002352:Carrier Proteins; D016755:Proto-Oncogene Proteins c-jun; D014665:Vasodilator Agents; C025090:ONO 1206; D000242:Cyclic AMP; D000527:Alprostadil