2010 Fiscal Year Final Research Report
Dysfunction of cystine/glutamate antiporter system in the hippocampus of epileptic rats
| Project/Area Number |
20591415
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | University of Miyazaki |
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Principal Investigator |
DOI Taku University of Miyazaki, 医学部, 助教 (70274793)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Yuto 宮崎大学, 医学部, 准教授 (70244192)
NAKAJIMA Akira 宮崎大学, 医学部, 教授 (10041857)
HUNAHASHI Hideki 宮崎大学, 医学部, 助教 (10404435)
EBIHARA Kosuke 宮崎大学, 医学部, 助教 (20510720)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 医歯薬学 |
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| Research Abstract |
Animals were injected 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM) and the nitroxide radicals were measured with microdialysis technique and an ESR analysis in the hippocampus. The antioxidant effect was measured to monitor sequential changes in the signal amplitude of nitroxide radical in the dialysate of both glutamate transporter inhibitor L-trans-pyrrolidine-2, 4-dicarboxylic acid (L-trans PDC) and control animals. The pattern showed exponential decay with median half-life of the nitroxide radical took significantly longer in the L-trans PDC group. And we performed qualitative analysis of redox state and cystine/glutamate exchanger (xCT) mRNA expression in the interictal state in the hippocampus of Fe^<+++>-induced epileptic rats. The expression of xCT mRNA in the ipsilateral hippocampus of Fe^<+++>-induced rats was decreased compared with controls. The half-life of nitroxide radical in Fe^<+++> group was statistically longer than that of control. The oxidative stress induced by the increased extracellular glutamate level through the suppression of glutamate transport activity results from transporters having a SH-redox modulatory site that is vulnerable to endogenous oxidants. Less cystine uptake induced by reduced xCT and increased extracellular glutamate leads to diminish of antioxidant glutathione, as a result reduces anti-oxidant ability. We conclude that collapse of glutamate regulation and antioxidant ability may be fundamental to Fe^<+++>-induced epileptogenesis.
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Research Products
(13 results)
