Down regulation of cerebellar serotonergic receptors in streptozotocin induced diabetic rats: Effect of pyridoxine and Aegle marmelose

Abstract

Oxidative stress plays an important role in cerebellar damage caused by diabetes, leading to deterioration in glucose homeostasis causing metabolic disorders. The present study was carried out to find the effects of Aegle marmelose leaf extract and insulin alone and in combination with pyridoxine on the cerebellar 5-HT through 5-HT(2A) receptor subtype, gene expression studies on the status of antioxidants-superoxide dismutase (SOD), glutathione peroxidase (GPx), 5-HT(2A) and 5-HT transporter (5-HTT) and immunohistochemical studies in streptozotocin induced diabetic rats. 5-HT and 5-HT(2A) receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in the cerebellum of diabetic rats compared to control. Gene expression studies of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum showed a significant down regulation (p<0.001) in diabetic rats compared to control. Pyridoxine treated alone and in combination with insulin, A. marmelose to diabetic rats reversed the B(max), K(d) of 5-HT, 5-HT(2A) and the gene expression of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Also, the Rotarod test confirms the motor dysfunction and recovery by treatment. These data suggest the antioxidant and neuroprotective role of pyridoxine and A. marmelose through the up regulation of 5-HT through 5-HT(2A) receptor in diabetic rats. Our results suggest that pyridoxine treated alone and in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalizing diabetic related oxidative stress and neurodegeneration affecting the motor ability of an individual by serotonergic receptors through 5-HT(2A) function. This has clinical significance in the management of diabetes.