본문 바로가기 주메뉴 바로가기
22대 대한민국 국회 국회정보길라잡이 국회의원검색
회원가입 로그인
HOME

정보검색

소장정보 검색

국회도서관 홈으로 정보검색 소장정보 검색

결과 내 검색

동의어 포함

고급검색

인명/단체명

저자정보 상세정보
인명/단체명을 입력하세요.

키워드

  • 대표어

  • 외국어

-

목차보기

Title Page 2

Abstract 5

Contents 7

Abbreviations 10

Ⅰ. Introduction 12

1. Brain functions 12

2. Alzheimer's disease 13

3. Limitations of animal models in Alzheimer's disease 14

4. Neural stem cells 15

5. Objective 16

Ⅱ. Materials and method 17

1. Cell culture 17

2. Double restriction enzyme digestion 17

3. Virus construction and production 18

4. Generation of AD-neural stem cells (AD-NSCs) 18

5. Co-culture of AD-NSCs and endothelial cells 19

6. Conventional PCR and qRT-PCR (Quantitative Real-Time PCR) 19

7. Immunocytochemistry 19

8. Statistical analysis 20

Ⅲ. Results 23

1. Generation of AD-neural stem cells overexpressing APP, PSEN1 and APP/PSEN1 23

2. Maintenance of neural stem cell characteristics in human fetal neural stem cells overexpressing Alzheimer's disease genes 26

3. Direct 2D in vitro model of neural stem cells and endothelial cells 28

4. Impaired neurogenesis and endothelial disruption in co-culture of AD-NSCs and endothelial cells 31

5. Tight junction disruption in endothelial cells co-cultured with AD-NSCs 34

Ⅳ. Discussion 37

Ⅴ. Reference 39

List of Tables 9

Table 1-1. Primers for RT-PCR and quantitative RT-PCR 21

Table 1-2. List of antibodies used for immunocytochemistry 22

List of Figures 8

Introduction 8

Figure 1-1. Functions of brain and AD neuropathological alterations 12

Figure 1-2. The processing of amyloidogenic pathway 13

Figure 1-3. Limitations of AD animal model 14

Figure 1-4. AD in vitro models 15

Results 8

Figure 1. Characterization of AD-neural stem cells (AD-NSCs) 25

Figure 2. Maintenance of neural stem cell characteristics in AD-NSCs 28

Figure 3. Direct 2D in vitro model and endothelial cell tight junction analysis 31

Figure 4. AD- NSCs impair the expression of TUJ1 and CD31 in direct 2D in vitro model 33

Figure 5. Disturbance of ZO-1 in endothelial cells co-cultured with AD-NSCs 36

초록보기

 Alzheimer's disease(AD) is a common neurodegenerative dementia, causing the cognitive impairment, memory loss and motor function problem. However, despite the increasing prevalence of dementia, the development of effective treatments remains challenging. Since animal models often fail to fully replicate the phenotypes of AD patients or exhibit different drug responses compared to humans. AD is pathologically identified by the deposition of amyloid beta peptides and neurofibrillary tangles (NFT) within the brain, which result in impaired neurogenesis and disruption of the blood-brain barrier (BBB). To replicate the pathophysiological mechanisms underlying AD, we generate AD-neural stem cells (AD-NSCs) by overexpressing AD-related genes with familial mutations, amyloid precursor protein (APP) and presenilin1 (PSEN1), in NSCs and co-culturing them withendothelial cells in 2D in vitro. As a result of overexpressing these genes, we observed an upregulation in the gene expression associated with the amyloidogenic pathway, including APP, BACE1, and PSEN1. This suggests the presence of a positive feedback loop like that observed in AD patients. Additionally, we noted a progressive impairment of neurogenesis and a decrease in the viability of endothelial cells over time in 2D in vitro model. Furthermore, we identified alteration in the expression of tight junction proteins, suggesting disruption of the BBB. Our 2D in vitro model successfully recapitulates key pathophysiological features of Alzheimer's disease, including progressive impairment of neurogenesis, decreased viability of endothelial cells, and alterations indicative of blood-brain-barrier disruption. This model offers a valuable platform for investigating AD pathophysiology and exploring novel therapeutic interventions.

추천서가 (다양한 추천 자료를 만나보세요)

권호기사보기

권호기사 목록 테이블로 기사명, 저자명, 페이지, 원문, 기사목차 순으로 되어있습니다.
기사명 저자명 페이지 원문 기사목차

권호

기사명 원문보기 기사목차
닫기