Neuroprotective role of curcumin in the cerebellum of streptozotocin-induced diabetic rats.
OBJECTIVE
Chronic hyperglycaemia in diabetes involves a direct neuronal damage caused by intracellular glucose which leads to altered neurotransmitter functions and reduced motor activity. The present study investigated the effect of curcumin in the functional regulation of muscarinic and alpha7 nicotinic acetylcholine receptors, insulin receptors, acetylcholine esterase and Glut3 in the cerebellum of streptozotocin (STZ)-induced diabetic rats.


METHODS
All studies were done in the cerebellum of male Wistar rats. Radioreceptor binding assays were done for total muscarinic, M(1) and M(3) receptors using specific ligands, and the gene expression was also studied using specific probes.


RESULTS
Our results showed an increased gene expression of acetylcholine esterase, Glut3, muscarinic M1, M3, alpha7 nicotinic acetylcholine and insulin receptors in the cerebellum of diabetic rats in comparison to control. Scatchard analysis of total muscarinic, M1 and M3 receptors showed an increased binding parameter, B(max) in diabetic rats compared to control. Curcumin and insulin inhibited diabetes-induced elevation in the gene expression of acetylcholine esterase, Glut3, insulin and cholinergic receptors in the cerebellum of diabetic rats.


CONCLUSIONS
Our studies suggest that curcumin plays a vital role in regulating the activity of cholinergic and insulin receptors and mechanism of glucose transportation through Glut3, which results in normalizing the diabetes-mediated cerebellar disorders. Thus, curcumin has a significant role in a therapeutic application for the prevention or progression of diabetic complications in the cerebellum.
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin - 682 022, Kerala, India.
Kumar T
KT
Peeyush
G
G
Gireesh
Mathew
M
Jobin
C S
CS
Paulose
D000110:Acetylcholinesterase / Q000096:biosynthesis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002531:Cerebellum / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008297:Male; D018696:Neuroprotective Agents; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects; D043643:Receptor, Muscarinic M1 / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D051274:Glucose Transporter Type 3; D018696:Neuroprotective Agents; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; C495690:Slc2a3 protein, rat; D011972:Receptor, Insulin; D000110:Acetylcholinesterase; D003474:Curcumin