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Aldose Reductase Deficiency Improves Wallerian Degeneration and Nerve Regeneration in Diabeticthy1-YFP Mice

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Bibliographic Details
Title: Aldose Reductase Deficiency Improves Wallerian Degeneration and Nerve Regeneration in Diabeticthy1-YFP Mice
Authors: Chung, SS, Chung, SK, Chen, YS
Source: Journal of Neuropathology & Experimental Neurology. 69:294-305
Publisher Information: Oxford University Press (OUP), 2010.
Publication Year: 2010
Subject Terms: Aldose reductase, Neural Conduction, Neovascularization, Physiologic, Mice, Transgenic, Diabetes Mellitus, Experimental, Axons - enzymology - pathology, Mice, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Aldehyde Reductase, Wallerian degeneration, Animals, Motor Neurons, Diabetic Neuropathies - enzymology - physiopathology - therapy, Macrophages, Diabetes, Axotomy, Recovery of Function, Axons, Nerve Regeneration, Nerve regeneration, Wallerian Degeneration - enzymology - physiopathology - therapy, Chemotaxis, Leukocyte, Disease Models, Animal, Nerve Regeneration - genetics, Aldehyde Reductase - deficiency - genetics, Sciatic Neuropathy, Wallerian Degeneration, Thy1-YFP mice
Description: This study examined the role of aldose reductase (AR) in diabetes-associated impaired nerve regeneration using thy1-YFP (YFP) mice. Sciatic nerves of nondiabetic and streptozotocin-induced diabetic AR(+/+)YFP and AR(-/-)YFP mice were transected after 4 weeks of diabetes. Wallerian degeneration and nerve regeneration were evaluated at 1 and 2 weeks postaxotomy by fluorescence microscopy. Motor nerve conduction velocity recovery and regenerating nerve morphometric parameters were determined at 10 and 20 weeks, respectively. There was no difference in the extent of Wallerian degeneration, size of regenerating stump, motor nerve conduction velocity recovery, or caliber of regenerating fibers between nondiabetic AR(+/+)YFP and AR(-/-)YFP mice. In diabetic AR(+/+)YFP mice, Wallerian degeneration was delayed, associated with slower macrophage invasion and abnormal vascularization. Those mice had smaller regenerating stumps, slower motor nerve conduction velocity, and smaller regenerating fibers compared with nondiabetic mice. These features of impaired nerve regeneration were largely attenuated in diabetic AR(-/-)YFP mice. Retarded macrophage invasion and vascularization associated with Wallerian degeneration were normalized in diabetic AR(-/-)YFP mice. These results indicate that AR plays an important role in diabetes-associated impaired nerve regeneration, in part by affecting vascularization and macrophage invasion during Wallerian degeneration. The thy1-YFP mice are valuable tools for further investigation of the mechanism of diabetes-associated nerve regeneration.
Document Type: Article
Language: English
ISSN: 1554-6578
0022-3069
DOI: 10.1097/nen.0b013e3181d26487
Access URL: https://academic.oup.com/jnen/article-pdf/69/3/294/17417856/69-3-294.pdf
https://pubmed.ncbi.nlm.nih.gov/20142761
https://academic.oup.com/jnen/article/69/3/294/2917270
http://hub.hku.hk/handle/10722/124477
https://pubmed.ncbi.nlm.nih.gov/20142761/
https://academic.oup.com/jnen/article-lookup/doi/10.1097/NEN.0b013e3181d26487
https://www.ncbi.nlm.nih.gov/pubmed/20142761
http://hdl.handle.net/10722/124477
Accession Number: edsair.doi.dedup.....9586e8243e06ee2a770a9a96125e26e7
Database: OpenAIRE
Description
Abstract:This study examined the role of aldose reductase (AR) in diabetes-associated impaired nerve regeneration using thy1-YFP (YFP) mice. Sciatic nerves of nondiabetic and streptozotocin-induced diabetic AR(+/+)YFP and AR(-/-)YFP mice were transected after 4 weeks of diabetes. Wallerian degeneration and nerve regeneration were evaluated at 1 and 2 weeks postaxotomy by fluorescence microscopy. Motor nerve conduction velocity recovery and regenerating nerve morphometric parameters were determined at 10 and 20 weeks, respectively. There was no difference in the extent of Wallerian degeneration, size of regenerating stump, motor nerve conduction velocity recovery, or caliber of regenerating fibers between nondiabetic AR(+/+)YFP and AR(-/-)YFP mice. In diabetic AR(+/+)YFP mice, Wallerian degeneration was delayed, associated with slower macrophage invasion and abnormal vascularization. Those mice had smaller regenerating stumps, slower motor nerve conduction velocity, and smaller regenerating fibers compared with nondiabetic mice. These features of impaired nerve regeneration were largely attenuated in diabetic AR(-/-)YFP mice. Retarded macrophage invasion and vascularization associated with Wallerian degeneration were normalized in diabetic AR(-/-)YFP mice. These results indicate that AR plays an important role in diabetes-associated impaired nerve regeneration, in part by affecting vascularization and macrophage invasion during Wallerian degeneration. The thy1-YFP mice are valuable tools for further investigation of the mechanism of diabetes-associated nerve regeneration.
ISSN:15546578
00223069
DOI:10.1097/nen.0b013e3181d26487