Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats.
Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, B(max) showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin-682022, Kerala, India.
T Peeyush
TP
Kumar
Sherin
S
Antony
G
G
Gireesh
Naijil
N
George
C S
CS
Paulose
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D010738:Type C Phospholipases; D003474:Curcumin; D004298:Dopamine