초록 ▼

본 연구에서는 AKAP12/Ninjnurin1 의 뇌 손상 보호 작용 및 분자적 조절 기전에 대한 연구를 수행하였다. MCAO, PT, EAE, TBI 등의 중추신경계 질환 모델을 확립하고 AKAP12 와 Ninjurin1의 발현 패턴을 확인하였으며, 이후 KO mice 와 zebrafish system을 사용하여 AKAP12와 Ninjurin1의 뇌혈관 장벽 보호와 관련된 역할들을 확인하였다. 추가 연구를 통해 이러한 작용을 매개하는 분자적 조절기전을 규명하였을 뿐 아니라, 정신질환, 면역질환으로 범위를 확대하여 AKAP12와

본 연구에서는 AKAP12/Ninjnurin1 의 뇌 손상 보호 작용 및 분자적 조절 기전에 대한 연구를 수행하였다. MCAO, PT, EAE, TBI 등의 중추신경계 질환 모델을 확립하고 AKAP12 와 Ninjurin1의 발현 패턴을 확인하였으며, 이후 KO mice 와 zebrafish system을 사용하여 AKAP12와 Ninjurin1의 뇌혈관 장벽 보호와 관련된 역할들을 확인하였다. 추가 연구를 통해 이러한 작용을 매개하는 분자적 조절기전을 규명하였을 뿐 아니라, 정신질환, 면역질환으로 범위를 확대하여 AKAP12와 Ninjurin1의 새로운 기능을 연구하였다. 또한 MPTP를 이용한 zebrafish 파킨슨 질환 모델을 확립하여 신경세포의 손상 회복에 관여하는 메커니즘을 규명하였다.

(출처 : 보고서 요약서 3p)

Abstract ▼

IV. Result

1st year: Characterization of AKAP12/Ninjurin1 expression under CNS diseases
∙ Establishment of mouse model for CNS diseases including MCAO, PT, and EAE
∙ Upregulation of AKAP12 expression in meninges after focal brain injury
∙ Expression of Ninjurin1 expression in immune

IV. Result

1st year: Characterization of AKAP12/Ninjurin1 expression under CNS diseases
∙ Establishment of mouse model for CNS diseases including MCAO, PT, and EAE
∙ Upregulation of AKAP12 expression in meninges after focal brain injury
∙ Expression of Ninjurin1 expression in immune cells during multiple sclerosis
∙ Upregulation of AKAP12 expression in damaged vessels of stroke model

2nd year: Establishment of KO mice system and investigation the role of AKAP12 in BBB stability and repair
∙ Establishment of AKAP12/Ninjurin1 KO mice
∙ Contribution of AKAP12 to brain repair by regulation of fibrotic-glial scar formation
∙ Maintenance of BBB stability by AKAP12 in zebrafish
∙ Inhibition of BBB damage by AKAP12 expressed in endothelial cell after stroke

3rd year: Investigation of the roles and regulatory molecular mechanisms of AKAP12/Ninjurin1 in the brain protection
∙ Regulation of BBB infiltration of immune cells through Ninjurin1-induced cell-cell interaction and cellular migration.
∙ Stimulation of AKAP12 expression TGF-β1 and Retinoic acid expressed in meninges
∙ AKAP12-mediated BBB protection through the inhibition of Rho activation after stroke

4th year: Establishment of additional CNS disease models and observation of neuronal defect in AKAP12/Ninjurin1 KO system
∙ Selective KO system of AKAP12 alpha and beta has been established and neurovascular defects by AKAP12 are revealed in zebrafish system
∙ OGD-like phenotype was found in over 3-month-old ninjurin1 KO mice and the relation between ninjurin1 and psychological disorder was investigated by several behavioral tests
∙ zebrafish Parkinson's disease model was established using neurotoxin MPTP
∙ Expression patterns of AKAP12 and Ninjurin1/2 were analyzed in TBI mice and AKAP12-dependent inhibition of pericyte cell death by OGD was studied

5th year: Investigation of disease-related mechanism of AKAP12/Ninjurin1 in CNS disease models
∙ Establishing the parkinson’s disease model in zebrafish using neurotoxin MPTP and investigating the behavioral patterns of nerve-injured zebrafish.
∙ Elucidating the role of AKAP12 in fibrotic scar that AKAP12 is gradually increased in fibrotic scar and inhibits the diffusion of macrophage via immune cell trapping structure in PT-induced mouse brain
∙ Identifying the expression of Ninjurin1 in thalamus and cortical layer neuron and less functional synapse and more glutamatergic neurotransmission activity in Ninjurin1 KO mouse.
∙ Ninjurin1 KO mice have an increased number of myeloid progenitor cells than WT mice, thus the myeloid progenitor cells can differentiate into macophage and microglia and trigger more inflammation.
∙ AKAP12 is expressed in brain pericyte and induce the differentiation of OPCs to oligodendrocyes.

6th year: Brain protection and repair by regulation of AKAP12/Ninjurin1 expression in CNS diseases
∙ Investigating inhibition of neuronal damages by HSP70 mRNA injection and the effect of ARD1 mediated HSP70 acetylation on neuronal protection in zebrafish Parkinson's disease model
∙ Analyzing behavioral abnormality of neuron-specific Ninjurin1 cKO mice Investigating a function of Ninjurin-1 in NMDA receptor activity
∙ Confirming apotosis- and immune polarization-mediated inhibition of immune cell activity in immune-trapping structure
∙ Establishment of mouse TBI model, controlled cortical impact (CCI) model and analyzing expression pattern of Ninjurin1 after TBI
∙ Identification of Ninjurin1 expressing cell types after TBI

(출처 : SUMMARY 8p)

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 요약서 ... 3
• 요약문 ... 4
• SUMMARY ... 7
• CONTENTS ... 11
• 목차 ... 12
• 제1장 연구개발과제의 개요 ... 13
• 제1절 연구개발의 목적 ... 13
• 제2절 연구개발의 필요성 ... 14
• 제3절 연구개발의 범위 ... 14
• 제2장 국내외 기술개발 현황 ... 15
• 제1절 국외 연구동향 ... 15
• 제2절 국내 연구동향 ... 15
• 제3장 연구개발수행 내용 및 결과 ... 16
• 제1절 연구 수행 방법 ... 16
• 제2절 연구 수행 결과 ... 17
• 제4장 목표달성도 및 관련분야에의 기여도 ... 95
• 제1절 연구개발목표의 달성도 ... 95
• 제2절 목표달성도에 대한 자체평가 ... 97
• 제3절 국내 연구인력 양성 결과 ... 100
• 제4절 해외기관과의 공동연구 성과 ... 101
• 제5장 연구개발결과의 활용계획 ... 115
• 제6장 연구개발과정에서 수집한 해외과학기술정보 ... 116
• 제7장 연구시설ㆍ장비 현황 ... 117
• 제8장 참고문헌 ... 120
• Final report for the GRL ... 122
• 끝페이지 ... 150