Muscarinic M1 and M3 Receptors,IP3 and cGMP Functional Regulation in Streptozotocin Induced Diabetic Rats: Insulin and Somatotropin Induced Rejuvenation as a Function of Age
Year: 2008
Type: dissertation
Abstract: The present study describes that acetylcholine through muscarinic Ml and\nM3 receptors play an important role in the brain function during diabetes as a function\nof age. Cholinergic activity as indicated by acetylcholine esterase, a marker for\ncholinergic function, decreased in the brain regions - the cerebral cortex, brainstem\nand corpus striatum of old rats compared to young rats. in diabetic condition, it was\nincreased in both young and old rats in cerebral cortex, and corpus striatum while in\nbrainstem it was decreased. The functional changes in the muscarinic receptors were\nstudied in the brain regions and it showed that muscarinic M I receptors of old rats\nwere down regulated in cerebral cortex while in corpus striatum and brainstem it was\nup regulated. Muscarinic M3 receptors of old rats showed no significant change in\ncerebral cortex while in corpus striatum and brainstem muscarinic receptors were\ndown regulated. During diabetes, muscarinic M I receptors were down regulated in\ncerebral cortex and brainstem of young rats while in corpus striatum they were up\nregulated. In old rats, M I receptors were up regulated in cerebral cortex, corpus\nstriatum and in brainstem they were down regulated. Muscarinic M3 receptors were\nup regulated in cerebral cortex and brainstem of young rats while in corpus striatum\nthey were down regulated. In old rats, muscarinic M l receptors were up regulated in\ncerebral cortex, corpus striatum and brainstem. In insulin treated diabetic rats the\nactivity of the receptors were reversed to near control. Pancreatic muscarinic M3\nreceptor activity increased in the pancreas of both young and old rats during diabetes.\nIn vitro studies using carbachol and antagonists for muscarinic Ml and M3 receptor\nsubtypes confirmed the specific receptor mediated neurotransmitter changes during\ndiabetes. Calcium imaging studies revealed muscarinic M I mediated Ca2\n+ release\nfrom the pancreatic islet cells of young and old rats. Electrophysiological studies\nusing EEG recording in young and old rats showed a brain activity difference during diabetes. Long term low dose STH and INS treated rat brain tissues were used for\ngene expression of muscarinic Ml, M3, glutamate NMDARl, mGlu-5,alpha2A, beta2,\nGABAAa1 and GABAB, DAD2 and 5-HT 2C receptors to observe the neurotransmitter\nreceptor functional interrelationship for integrating memory, cognition and\nrejuvenating brain functions in young and old. Studies on neurotransmitter receptor\ninteraction pathways and gene expression regulation by second messengers like IP3\nand cGMP in turn will lead to the development of therapeutic agents to manage\ndiabetes and brain activity.From this study it is suggested that functional improvement of\nmuscarinic Ml, M3, glutamate NMDAR1, mGlu-5, alpha2A, beta2, GABAAa1 and GABAB,\nDAD2 and 5-HT 2C receptors mediated through IP3 and cGMP will lead to therapeutic\napplications in the management of diabetes. Also, our results from long term low dose\nSTH and INS treatment showed rejuvenation of the brain function which has clinical\nsignificance in maintaining healthy period of life as a function of age.
Authors: Savitha Balakrishnan, C.S. Paulose
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1587264386