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.
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 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.
Article: Effects of exogenous galanin on neuropathic pain state and change of galanin and its receptors in DRG and SDH after sciatic nerve-pinch injury in rat.[show abstract] [hide abstract]
ABSTRACT: A large number of neuroanatomical, neurophysiologic, and neurochemical mechanisms are thought to contribute to the development and maintenance of neuropathic pain. However, mechanisms responsible for neuropathic pain have not been completely delineated. It has been demonstrated that neuropeptide galanin (Gal) is upregulated after injury in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) where it plays a predominantly antinociceptive role. In the present study, sciatic nerve-pinch injury rat model was used to determine the effects of exogenous Gal on the expression of the Gal and its receptors (GalR1, GalR2) in DRG and SDH, the alterations of pain behavior, nerve conduction velocity (NCV) and morphology of sciatic nerve. The results showed that exogenous Gal had antinociceptive effects in this nerve-pinch injury induced neuropathic pain animal model. It is very interesting that Gal, GalR1 and GalR2 change their expression greatly in DRG and SDH after nerve injury and intrathecal injection of exougenous Gal. Morphological investigation displays a serious damage after nerve-pinch injury and an amendatory regeneration after exogenous Gal treatment. These findings imply that Gal, via activation of GalR1 and/or GalR2, may have neuroprotective effects in reducing neuropathic pain behaviors and improving nerve regeneration after nerve injury.PLoS ONE 01/2012; 7(5):e37621. · 4.09 Impact Factor