Abstract ▼

□ Purpose&contents
Purpose: This study was done to understand the role of glutathione peroxidase-1(GPx1) gene in the excitotoxicity and memory impairment induced by kainic acid. Contets:
- Time-dependent changes in GPx1 expression and GPx activity after epileptic seizures induced by intracereb

□ Purpose&contents
Purpose: This study was done to understand the role of glutathione peroxidase-1(GPx1) gene in the excitotoxicity and memory impairment induced by kainic acid. Contets:
- Time-dependent changes in GPx1 expression and GPx activity after epileptic seizures induced by intracerebroventricular kainate in the hippocampus of mice.
- Evaluation of kainate-induced seizure, neurotoxicity and memory impairment in GPx1 gene knockout (KO) and GPx1 gene overexpressing transgenic (Tg) mice.
- Study on the mechanism of GPx1-related signaling pathway in various excitotoxic conditions.
- Pharmacological evaluation of the GPx-inducing antioxidants in these conditions.

□ Result
- Convulsive dose of kainate decreased GPx1 protein expression, but increased GPx1 mRNA expression and GPx activity in the hippocampus, in a time-dependent manner. In situ GPx activity could be dependent on the substrate concentrate, then GSH-GSSG recycling was decreased after kainate injection.
- Both GPx1 KO and GPx1 Tg attenuated kainate-induced seizure and neurotoxicity as compared to wild-type mice. This attenuation was less pronounced in aged mice with higher level of physiological oxidative stress.
- Ceruloplasmin plays a protective role in the kainate-induced excitotoxicity via activation of Nrf2 signaling pathway and up-regulation of the expression of glutathione-synthesizing enzymes.
- PKCδ, an oxidative stress-sensitive kinase, mediates trimethyltin (TMT)-induced excitotoxicity through the regulation of PI3K/Akt pathway, and we obtained the result suggesting the crosstalk between PKCδ and GPx1 in this model.
- GPx1 KO potentiated, but GPx1 Tg attenuated the memory impairment and consequent changes in signal molecules induced by sub-convulsive dose of kainate.
- Melatonin showed profound neuroprotective and GPx1 inducing effects in response to kainate-induced excitotoxicity. In addition, melatonin attenuated the memory impairment, oxidative stress and changes in antioxidant status induced by sub-convulsive dose of kainate.

□ Expected Contribution
- Intensified study will be performed on the role and mechanism of GPx1, ceruloplasmin, PKCδ, and Interleukin-6 in various animal models including kainate, TMT, and microcystin models.
- The result from this project can provide valuable information to understand pathophysiological mechanism and to develop potential therapeutic candidates for epileptic seizures and following memory impairments.
- Animal models established in this project will be halpful for further studies after validation.

( 출처 : SUMMARY 5p )

목차 Contents

• 표지 ... 1
• 목차 ... 2
• 연구계획 요약문 ... 3
• 연구결과 요약문 ... 4
• 한글요약문 ... 4
• SUMMARY ... 5
• 연구내용 및 결과 ... 6
• 1. 연구개발과제의 개요 ... 6
• 2. 국내외 기술개발 현황 ... 10
• 3. 연구수행 내용 및 결과 ... 11
• 4. 목표달성도 및 관련분야에의 기여도 ... 30
• 5. 연구결과의 활용계획 ... 33
• 6. 연구과정에서 수집한 해외 과학기술정보 ... 34
• 7. 참고문헌 ... 35
• 8. 연구성과 ... 40
• 9. 국가과학기술지식정보서비스에 등록한 연구시설‧장비 현황 ... 43
• 10. 연구개발과제 수행에 따른 연구실 등의 안전조치 이행실적 ... 44
• 11. 기타사항 ... 46
• 끝페이지 ... 46