- 作者: G Gireesh; T Peeyush Kumar; Jobin Mathew; C S Paulose
- 作者服務機構: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin, Kerala, India
- 中文摘要: --
- 英文摘要:
Acetylcholine (ACh), the first neurotransmitter to be identified, regulate the activities of central
and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic
acetylcholine receptor (mAChR) have been implicated in the pathophysiology of many major
diseases of the central nervous system (CNS). Previous reports from our laboratory on
streptozotocin (STZ) induced diabetic rats showed down regulation of muscarinic M1 receptors
in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have
investigated the changes of acetylcholine esterase (AChE) enzyme activity, total muscarinic and
muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ - diabetic rats
and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in
motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has
complex and clinically important actions in the striatum that are mediated predominantly by
muscarinic receptors. We observed that insulin treatment brought back the decreased maximal
velocity (Vmax) of acetylcholine esterase in the corpus striatum during diabetes to near control
state. In diabetic rats there was a decrease in maximal number (Bmax) and affinity (Kd) of total
muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity
in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near
control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the
increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment.
These results suggest the diabetes-induced changes of the cholinergic activity in the corpus
striatum and the regulatory role of insulin on binding parameters and gene expression of total
and muscarinic M1 receptors. - 中文關鍵字: --
- 英文關鍵字: --