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.
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 Talpha1 alpha-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 betaIII 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.
Shimoshige
Yukinori
Y
Pharmacology Research Labs, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan. yukinori.shimoshige@jp.astellas.com
Enomoto
Ryugo
R
Aoki
Toshiaki
T
Matsuoka
Nobuya
N
Kaneko
Shuji
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D011108:Polymers; D011799:Quinazolines; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D014404:Tubulin; C024617:polyol; C051774:neurofilament protein H; C064920:FR 74366; D000449:Aldehyde Reductase