2006 Fiscal Year Final Research Report Summary
The functional role of glutamate transporter associated protein (GTRAP3-18) in epileptogenesis
| Project/Area Number |
17591223
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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, Faculty of Medicine, Assistant, 医学部, 助手 (70274793)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Yuto University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (70244192)
NAKAJIMA Akira University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (10041857)
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| Project Period (FY) |
2005 – 2006
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| Keywords | epilepsy / glutamate / GABA / transporter / GTRAP3-18 / addicsin |
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| Research Abstract |
EAAC-1 functions in the re-uptake of extracellular glutamate that leads to synthesis of GABA. Knockdown of EAAC-1 by anti-sense induces convulsive seizures in rats. Glutamate transporter associated protein 3-18 (GTRAP3-18) suppresses the binding affinity of glutamate with EAAC1 on the neuron. We undertook this study to evaluate the contribution of GTRAP3-18 in the PTZ kindling. Rats were injected with GTRAP3-18 anti-sense oligonucleotide into lateral ventricle, after that the animals were administered i.p. three times per week with PTZ (40 mg/kg) until they were fully kindled. Measurement of hippocampal glutamate and GABA transporters and glutamate receptors by western blot showed that GLT-1, GAT-3, GluR1, G1uR2, NMDAR1 were decreased significantly at 24 hours in fully kindled GTRAP3-18 knockdown compared to control (injected sense oligonucleotide and fully kindled). PTZ seizure duration was significantly prolonged, latency more brief and kindling onset earlier when compared to control animals. The microdialysis study show that hippocampal glutamate and GABA basal release in GTRAP3-18 knockdown group higher rather than those of senseinjected group. These observations suggest that GTRAP3-18 may affect development of epileptogenesis.
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