Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: Neuroprotective role of pyridoxine and Aegle marmelose

Diabetes and stress stimulate hippocampal 5-ht synthesis,metabolism and release. the present study was carried out to find the effects of insulin,aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-ht,5-ht2a receptor subtype,gene expression studies on 5-ht 2a,5-htt,insr,immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 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 b max showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in kd in hippocampus 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 in combination with insulin and a. marmelose to diabetic rats reversed the 5-ht content,bmax,k dof 5-ht,5-ht2aand gene expression of 5-ht2a,5-htt and insr in hippocampus to near control. the gene expression of 5-ht 2a 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. our 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. © 2010 abraham et al; licensee biomed central ltd.