Diabetes is not a potent inducer of neuronal cell death in mouse sensory ganglia, but it enhances neurite regeneration in vitro.
We examined the effects of diabetes on the morphological features and regenerative capabilities of adult mouse nodose ganglia (NG) and dorsal root ganglia (DRG). By light and electron microscopy, no apoptotic cell death was detected in the ganglia obtained from either streptozotocin (STZ)-induced diabetic or normal C57BL/6J mice in vivo. Neurite regeneration from transected nerve terminals of NG and DRG explants in culture at normal (10 mM) and high (30 mM) glucose concentrations was significantly enhanced in the diabetic mice. Chromatolytic changes (i.e. swelling and migration of the nucleus to an eccentric position in the neurons, and a loss of Nissl substance in the neuronal perikarya) and apoptotic cell death (less than one-fifth of the neurons) in the cultured ganglia were present, but neither hyperglycemia in vivo nor high glucose conditions in vitro altered the morphological features of the ganglia or the ratios of apoptotic cells at 3 days in culture. By semiquantitative RT-PCR analysis, the mRNA expressions of ciliary neurotrophic factor (CNTF) in DRG from both mice were down-regulated at 1 day in culture. The expression in diabetic DRG, but not in control DRG, was significantly up-regulated at later stages (3 and 7 days) in culture. In summary, hyperglycemia is unlikely to induce cell death in the sensory ganglia, but enhances the regenerative capability of vagal and spinal sensory nerves in vitro. The up-regulation of CNTF mRNA expression during the culture of diabetic DRG may play a role in the enhanced neurite regeneration.
Sango
Kazunori
K
Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, 183-8526, Tokyo, Japan. kazsango@tmin.ac.jp
Horie
Hidenori
H
Saito
Haruhiro
H
Ajiki
Kyoko
K
Tokashiki
Akiko
A
Takeshita
Kaori
K
Ishigatsubo
Yoshiaki
Y
Kawano
Hitoshi
H
Ishikawa
Yoshihiro
Y
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D020934:Ciliary Neurotrophic Factor / Q000235:genetics; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015536:Down-Regulation; D005260:Female; D017950:Ganglia, Sensory / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration; D016501:Neurites; D009474:Neurons / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin
D020934:Ciliary Neurotrophic Factor; D017931:DNA Primers; D012333:RNA, Messenger; D013311:Streptozocin