The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.
Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes.
Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.
Antony
A
Sherin
Kumar T
KT
Peeyush
George
G
Naijil
Mohan Sobhana
MS
Nandhu
Sadanandan
S
Jayanarayanan
Paul
P
Jes
Cheramadathikudiyil Skaria
CS
Paulose
D000818:Animals; D001285:Atropine / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation; D051274:Glucose Transporter Type 3 / Q000235:genetics; D006706:Homeostasis; D007003:Hypoglycemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000235:genetics* / Q000378:metabolism*
D001786:Blood Glucose; D051274:Glucose Transporter Type 3; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D001285:Atropine; D002795:Choline O-Acetyltransferase