Decreased muscarinic M1 receptor gene expression in the cerebral cortex of streptozotocin-induced diabetic rats and Aegle marmelose leaf extract's therapeutic function

Gangadharan, Gireesh; Reas, S. Khan; Mathew, Joseph; Paulose, C S

doi:10.1016/j.jep.2007.11.036

Cited by 19 publications

(11 citation statements)

References 54 publications

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“…Hypoglycemia has been reported to cause neuronal dysfunction. Previous studies from our laboratory, have reported the altered neurotransmitter receptor status during diabetes, was brought back to normal during optimal dosage of insulin therapy whereby increased blood glucose level during diabetes is brought back to near normal (Gireesh et al 2008). Glutamatergic and dopaminergic receptor functional deficit associated with hypoglycemia and diabetic hyperglycemia (Robinson et al 2009) and cholinergic neuronal dysfunction in the cerebellar region is reported in our previous research (Antony et al 2010).…”

Section: Discussionmentioning

confidence: 64%

Decreased Cholinergic Receptor Expression in the Striatum: Motor Function Deficit in Hypoglycemic and Diabetic Rats

et al. 2011

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Hypoglycemic brain injury is a common and serious complication of insulin therapy associated with diabetes. This study evaluated the effect of insulin-induced hypoglycemia and STZ-induced diabetes on striatal cholinergic receptors and enzyme expression and on motor function. Cholinergic enzymes: AChE and ChAT gene expression, radioreceptor binding assay and immunohistochemistry of muscarinic M1, M3 receptors and α7nAChR were carried out. Motor performance on grid walk test was analysed. AChE and ChAT expression significantly downregulated in hypoglycemic and diabetic rats. Total muscarinic and Muscarinic M3 receptor binding decreased in hypoglycemic rats compared to diabetic rats whereas muscarinic M1 receptor binding increased in hypoglycemic rats compared to diabetic rats. Real-time PCR analysis and confocal imaging of muscarinic M1, M3 receptors confirmed the changes in muscarinic receptor binding in hypoglycemic and diabetic rats. In hypoglycemic rats, α7nAChR expression significantly up regulated compared to diabetic rats. Grid walk test demonstrated the impairment in motor function and coordination in hypoglycemic and hyperglycemic rats. Neurochemical changes along with the behavioral data implicate a role for impaired striatal cholinergic receptor function inducing motor function deficit induced by hypo and hyperglycemia. Hypoglycemia exacerbated the neurobehavioral deficit in diabetes which has clinical significance in the treatment of diabetes.

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Section: Discussionmentioning

confidence: 64%

Decreased Cholinergic Receptor Expression in the Striatum: Motor Function Deficit in Hypoglycemic and Diabetic Rats

et al. 2011

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“…Previous reports show that diabetes mellitus specifically impair the memory function in experimental animals with strong involvement of the hippocampus and cerebral cortex [25]. Earlier works from our laboratory on neurochemical changes induced by diabetes showed cholinergic deficit in brain regions like cerebral cortex, cerebellum [26,27] causing cognitive dysfunction in diabetic rats. Present study analysed brainstem Cholinergic, Insulin, Vitamin D receptors and GLUT 3 gene expression is affected by diabetes and Vitamin D supplementation could modulate the brainstem receptors.…”

Section: Discussionmentioning

confidence: 92%

Expression of Cholinergic, Insulin, Vitamin D Receptors and GLUT 3 in the Brainstem of Streptozotocin Induced Diabetic Rats: Effect of Treatment with Vitamin D3

et al. 2011

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Complications arising from diabetes mellitus include cognitive deficits, neurophysiological and structural changes in the brain. The current study investigated the expression of cholinergic, insulin, Vitamin D receptor and GLUT 3 in the brainstem of streptozotocin-induced diabetic rats. Radioreceptor binding assays and gene expression were done in the brainstem of male Wistar rats. Our results showed that B(max) of total muscarinic, muscarinic M3 receptors was increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. A significant increase in gene expression of muscarinic M3, α7 nicotinic acetylcholine, insulin, Vitamin D₃ receptors, acetylcholine esterase, choline acetyl transferase and GLUT 3 were observed in the brainstem of diabetic rats. Immunohistochemistry studies of muscarinic M1, M3 and α7 nicotinic acetylcholine receptors confirmed the gene expression at protein level. Vitamin D₃ and insulin treatment reversed diabetes-induced alterations to near control. This study provides an evidence that diabetes can alter the expression of cholinergic, insulin, Vitamin D receptors and GLUT 3 in brainstem. We found that Vitamin D₃ treatment could modulate the Vitamin D receptors and plays a pivotal role in maintaining the glucose transport and expressional level of cholinergic receptors in the brainstem of diabetic rats. Thus, our results suggest a therapeutic role of Vitamin D₃ in managing neurological disorders associated with diabetes.

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“…Administration of AME was found to decrease the FBG and total cholesterol significantly as compared to the untreated diabetic animals. AME is postulated to increase the uptake of glucose by increasing the insulin release and inducing the synthesis of insulin (Gireesh et al, 2008). The plant is also documented to help in regeneration of the damaged pancreas in diabetic rats and decrease the blood cholesterol levels (Das et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Ameliorative effect ofAegle marmelosleaf extract on early stage alloxan-induced diabetic cardiomyopathy in rats

Bhatti¹,

Sharma²,

Singh³

et al. 2011

Pharmaceutical Biology

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Decreased muscarinic M1 receptor gene expression in the cerebral cortex of streptozotocin-induced diabetic rats and Aegle marmelose leaf extract's therapeutic function

Cited by 19 publications

References 54 publications

Decreased Cholinergic Receptor Expression in the Striatum: Motor Function Deficit in Hypoglycemic and Diabetic Rats

Decreased Cholinergic Receptor Expression in the Striatum: Motor Function Deficit in Hypoglycemic and Diabetic Rats

Expression of Cholinergic, Insulin, Vitamin D Receptors and GLUT 3 in the Brainstem of Streptozotocin Induced Diabetic Rats: Effect of Treatment with Vitamin D3

Ameliorative effect ofAegle marmelosleaf extract on early stage alloxan-induced diabetic cardiomyopathy in rats

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