title: Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.
abstract: 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 Kd showed a significant decrease (p < 0.001) whereas 5-HT(2A) receptor binding parameters Bmax 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-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), Kd 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.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin- 682 022, Kerala, India.
authors.forename: Pretty Mary
authors.initials: PM
authors.lastname: Abraham
authors.forename: Korah P
authors.initials: KP
authors.lastname: Kuruvilla
authors.forename: Jobin
authors.initials: J
authors.lastname: Mathew
authors.forename: Anitha
authors.initials: A
authors.lastname: Malat
authors.forename: Shilpa
authors.initials: S
authors.lastname: Joy
authors.forename: C S
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D045471:Aegle / Q000737:chemistry*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009483:Neuropsychological Tests; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D011736:Pyridoxine / Q000378:metabolism / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013311:Streptozocin; D013312:Stress, Physiological; D014803:Vitamin B Complex / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D010936:Plant Extracts; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; D014803:Vitamin B Complex; D012701:Serotonin; D013311:Streptozocin; D011972:Receptor, Insulin; D011736:Pyridoxine