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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-HT 2A  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 B max  and K d  showed a significant decrease ( p  < 0.001) whereas 5-HT 2A  receptor binding parameters B max  showed a significant decrease ( p  < 0.001) with a significant increase ( p  < 0.05) in K d  in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT 2A,  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, B max  , K d  of 5-HT, 5-HT 2A  and gene expression of 5-HT 2A , 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.

journal of biomedical science

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