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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.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Jayanarayanan S,Smijin S,Peeyush KT,Anju TR,Paulose CS

doi

10.1016/j.cbi.2012.11.024

subject

Has Abstract

pub_date

2013-01-25 00:00:00

pages

39-48

issue

1-3

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(12)00270-0

journal_volume

201

pub_type

杂志文章

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