Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

The most and well known effects of diabetes mellitus on CNS is dysfunction of neurotransmitters, which is secondary to the metabolic disorders such as hyperglycemia and acidosis. It has been proposed that an unbalanced autonomic nervous system may be a major cause of the metabolic syndrome [1] Diabetes mellitus have also been reported to be accompanied by a number of behavioral and hormonal abnormalities, including hyperphagia, reduced motor activity [2,3]. CNS abnormalities including neuronal atrophy and axonal degenerations [4,5] are also associated with diabetes. The altered levels of neurotransmitter in specific brain areas in patients with diabetes mellitus [6] and in animals with experimental diabetes [7-12] have been documented and implicated in the CNS disorders. ACh, a major neurotransmitter from autonomic nervous system, regulates the cholinergic stimulation of insulin secretion, through interactions with muscarinic receptors. Recently we have reported that muscarinic M1 receptor gene expressions were decreased in the cerebral cortex, brainstem, hypothalamus and pancreatic islets of STZ induced diabetic rats and insulin modulates the binding parameters and gene expression [13,14]. Acetylcholine muscarinic receptors, members of the superfamily of G protein-coupled receptors, are classified pharmacologically into M1 to M5 subtypes, with M1, M3 and M5 receptors preferentially coupling to Gαq/11 proteins and M2 and M4 receptors to Gαi/o proteins [9]. All five muscarinic receptors are expressed by striatal neurones, with M1 and M4 receptors as the predominant subtypes, conforming together nearly 80% of the receptor population in the rat as shown by immunodetection [15,16] The main objective of the present study was to determine whether uncontrolled hyperglycemia, as a consequence of diabetes, altered the acetylcholine esterase enzyme activity, total and muscarinic M1 receptor binding parameters and muscarinic M1 receptor gene expression and the regulatory role