Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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The Involvement of Aldose Reductase in Alterations to Neurotrophin Receptors and Neuronal Cytoskeletal Protein mRNA Levels in the Dorsal Root Ganglion of Streptozotocin-Induced Diabetic Rats
Yukinori ShimoshigeRyugo EnomotoToshiaki AokiNobuya MatsuokaShuji Kaneko
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2010 Volume 33 Issue 1 Pages 67-71

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Abstract

Dorsal root ganglia (DRG) are recognized as one of the organs which are damaged in peripheral sensory diabetic neuropathy. In an experimental animal model, the alteration of the mRNA expression level of neurotrophins, their receptors and neuronal cytoskeletal protein have been reported. In this study, we examined whether these changes are improved by treatment with the aldose reductase inhibitor, zenarestat, in early-stage diabetic neuropathy of streptozotocin (STZ)-induced diabetic rats. Two weeks after the induction of diabetes mellitus by STZ treatment, zenarestat or a vehicle were given orally for two weeks. After the zenarestat treatment, the mRNA expression levels of neurotrophin receptors and neuronal cytoskeletal proteins in dorsal root ganglia were determined with a real-time polymerase chain reaction (PCR) method. Compared with the expression level of normal rats, a significant increase in Trk-C and Tα1 α-tubulin and a decrease in neurofilament H mRNA expression level were observed in the DRG of STZ rats, while there were no significant changes in Trk-A, Trk-B, p75, neurofilament L, neurofilament M and βIII tubulin mRNA expression. Zenarestat treatment significantly ameliorated the abnormal increase in Trk-C mRNA expression level. These data suggest that hyperactivation of the polyol pathway induces a deficit in neurotropism on peripheral sensory diabetic neuropathy.

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© 2010 The Pharmaceutical Society of Japan
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