title: NMDA and AMPA receptor mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rat: ameliorating effects of curcumin.
abstract: Functional activity of neurotransmitter receptor and their sensitivity to regulation are altered in DM. We evaluated the neuroprotective effect of curcumin in glutamate mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rats. Gene expression studies in diabetic rats showed a down regulation of glutamate decarboxylase mRNA leading to accumulation of glutamate. Radioreceptor binding assays showed a significant increase in α-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptors density which was confirmed by immunohistochemical studies. Decreased glutathione peroxidases gene expression indicates enhanced oxidative stress in diabetic rats. This leads to decreased expression of glutamate aspartate transporter, which in turn reduces glutamate transport. All these events lead to excitotoxic neuronal death in the cerebral cortex, which was confirmed by the increased expression of caspase 3, caspase 8 and BCL2-associated X protein. Curcumin and insulin treatment reversed these altered parameters to near control. We establish, a novel therapeutic role of curcumin by reducing the glutamate mediated excitotoxicity in cerebral cortex of diabetes through modulating the altered neurochemical parameters.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin 682022, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Jayanarayanan
authors.forename: S
authors.initials: S
authors.lastname: Smijin
authors.forename: K T
authors.initials: KT
authors.lastname: Peeyush
authors.forename: T R
authors.initials: TR
authors.lastname: Anju
authors.forename: C S
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; D020169:Caspases; D005968:Glutamate Decarboxylase; D003474:Curcumin