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Delayed initiation of regeneration in diabetic nerve is preceded by attenuation of immediate early gene responses
Journal of Diabetes and Its Complications 15 (2001) 18
Abstract Delayed initiation of regeneration in diabetic nerve is preceded by attenuation of immediate early gene responses Xu G., Jiang H.Y., Shy M.E., Sima A.A.F. Department of Pathology, Wayne State University School of Medicine, 540 East Canfield Avenue, G.H. Scott Hall of Basic Medical Science, Detroit, MI 48201, USA. Nerve fiber regeneration is impaired in diabetic nerve and contributes to the relentless nerve fiber loss that characterizes this disorder. Immediate early gene responses constitute the initial response to nerve injury and include upregulation of NGF and IGF-1 primarily by Schwann cells. These responses are believed to initiate the macrophage recruitment necessary for the initiation of axonal regeneration. We examined NGF, IGF-1, and CNTF
mRNA expression in sciatic nerve at 10 timepoints (0.5 h to 24 days) following sciatic nerve crush injury in diabetic BB/W rats. The peak of the immediate upregulation of IGF-1 and NGF occurred at 0.5 and 6 h, respectively, in control rats and was delayed to 24 h for both IGF-1 and NGF in diabetic nerves. Also the expression of NGF p75 receptor was significantly attenuated in diabetic nerves. CNTF mRNA showed an immediate downregulation following nerve crush with no significant differences between control and diabetic rats. These findings suggest that attenuations of the immediate gene responses of para- and autocrine IGF-1 and NGF in diabetic nerve may be responsible for the earlier reported defect in macrophage recruitment and delayed initiation of nerve fiber regeneration. This study was supported by the Thomas Foundation and JDFI.
1056-8727/01/$ ± see front matter D 2001 Elsevier Science Inc. All rights reserved. PII: S 1 0 5 6 - 8 7 2 7 ( 0 0 ) 0 0 0 9 9 - 4
Abstract Delayed initiation of regeneration in diabetic nerve is preceded by attenuation of immediate early gene responses Xu G., Jiang H.Y., Shy M.E., Sima A.A.F. Department of Pathology, Wayne State University School of Medicine, 540 East Canfield Avenue, G.H. Scott Hall of Basic Medical Science, Detroit, MI 48201, USA. Nerve fiber regeneration is impaired in diabetic nerve and contributes to the relentless nerve fiber loss that characterizes this disorder. Immediate early gene responses constitute the initial response to nerve injury and include upregulation of NGF and IGF-1 primarily by Schwann cells. These responses are believed to initiate the macrophage recruitment necessary for the initiation of axonal regeneration. We examined NGF, IGF-1, and CNTF
mRNA expression in sciatic nerve at 10 timepoints (0.5 h to 24 days) following sciatic nerve crush injury in diabetic BB/W rats. The peak of the immediate upregulation of IGF-1 and NGF occurred at 0.5 and 6 h, respectively, in control rats and was delayed to 24 h for both IGF-1 and NGF in diabetic nerves. Also the expression of NGF p75 receptor was significantly attenuated in diabetic nerves. CNTF mRNA showed an immediate downregulation following nerve crush with no significant differences between control and diabetic rats. These findings suggest that attenuations of the immediate gene responses of para- and autocrine IGF-1 and NGF in diabetic nerve may be responsible for the earlier reported defect in macrophage recruitment and delayed initiation of nerve fiber regeneration. This study was supported by the Thomas Foundation and JDFI.
1056-8727/01/$ ± see front matter D 2001 Elsevier Science Inc. All rights reserved. PII: S 1 0 5 6 - 8 7 2 7 ( 0 0 ) 0 0 0 9 9 - 4