Pretty Mary Abraham
University of Chicago, USA
Title: Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: Neuroprotective role of pyridoxine and Aegle marmelose
Biography
Biography: Pretty Mary Abraham
Abstract
Introduction: Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. Objective: Study was conducted to see the prevalence, the adverse effects of stress, etiology and course of the diabetes through serotonergic system. Methods: Hippocampal concentrations of 5-HT and 5-HIAA using HPLC, 5-HT through 5HT2A receptor binding, 5-HTT and INSR gene expression using real-time PCR and immunohistochemical studies using confocal microscope was carried out. Behavioural studies using elevated-plus maze was also done. Results: 5-HT content showed a significant decrease (p<0.001) and a significant increase (p<0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p<0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p<0.001) with an increase (p<0.05) in Kd of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p<0.001) in diabetic rats compared to control. Pyridoxine treated with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax, Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. Gene-expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p<0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Conclusion: Results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.