Decreased muscarinic M1 receptor gene expression in the cerebral cortex of streptozotocin-induced diabetic rats and Aegle marmelose leaf extract's therapeutic function

Aim: In the present study we have investigated the changes in the total muscarinic and muscarinic M1 receptor ([H-3]QNB) binding and gene expression in the cerebral cortex of streptozotocin (STZ) induced diabetic, insulin and aqueous extract of Aegle marmelose leaf treated diabetic rats. Materials and Methods: Diabetes was induced in rats by intrafemoral injection of streptozotocin. Aegle marmelose leaves was given orally to one group of rats at a dosage of 1 g/kg body weight per day for fourteen days. Blood glucose and plasma insulin level were measured. Muscarinic and Muscarinic M1 receptor binding studies were done in the cerebral cortex of experimental rats. Muscarinic M1 receptor gene expression was studied using real-time PCR. Results: Scatchard analysis for total muscarinic receptors in cerebral cortex showed that the B-max was decreased significantly (p < 0.001) in diabetic rats with a significant decrease (p<0.01) in the K-d when compared to control group. Binding analysis of Muscarinic M1 receptors showed that B-max was decreased significantly (p < 0.001) in diabetic group when compared to control group. The Kd also decreased significantly (p < 0.01) when compared to control group. The binding parameters were reversed to near control by the treatment of diabetic rats with Aegle marmelose. Real-Time PCR analysis also showed a similar change in the mRNA levels of muscarinic M1 receptors. Conclusion: The results showed that there is decrease in total muscarinic and muscarinic M1 receptors during diabetes which is up regulated by insulin and Aegle marmelose leaf extract treatment. This has clinical significance in therapeutic management of diabetes. (C) 2007 Elsevier Ireland Ltd. All rights reserved.