Project/Area Number |
22700332
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Neuroscience in general
|
Research Institution | University of Toyama |
Principal Investigator |
INOUE Ran 富山大学, 大学院・医学薬学研究部(医学), 助教 (70401817)
|
Project Period (FY) |
2010 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 分子 / 細胞神経科学 / D-セリン / セリンラセマーゼ / NMDA受容体 / てんかん / NDMA受容体 |
Research Abstract |
In this study, we examined the effect of D-serine deficiency on the seizures induced by a single injection of pentylenetetrazole(PTZ) using SR knockout(KO) mice. We found that, compared with wild-type(WT) mice, SR-KO mice showed the attenuation of seizure expression in terms of a significantly shortened duration of generalized seizures and resistance to generalized clonic-tonic seizures. Consistently, immunohistochemical analysis of c-Fos demonstrated that the level of c-Fos labeling induced by high-dose PTZ in the cerebral cortex, hippocampal CA1, hippocampal CA3, and the basolateral nucleus of the amygdala in WT mice was significantly higher than that in SR-KO mice. Moreover, PTZ induced an increase in extracellular glutamate level in the dentate gyrus of WT mice at two different time phases. However, such a PTZ-induced increase in glutamate level was completely inhibited in SR-KO mice. The present findings suggest that SR may be a target for the development of new therapeutic strategies for epileptic seizures.
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