표제지
목차
국문요약 11
Ⅰ. 서론 13
1. 우리나라 고령 인구 추이 및 원인별 사망률 13
2. 알츠하이머병의 정의 및 증상 15
3. 알츠하이머병의 병리학적 특징 16
4. 인삼이 알츠하이머병에 미치는 영향 24
5. 프로바이오틱스가 알츠하이머병에 미치는 영향 25
6. 인지기능 손상 및 치료에 사용되는 약물 26
7. 연구 목적 27
Ⅱ. 연구내용 및 방법 28
1. 실험 재료 28
2. 인간 신경모세포종 배양 29
3. 산화스트레스에 대한 신경세포 보호 29
4. 동물사육 30
1) 실험동물 및 실험디자인 30
2) 식이섭취량 및 장기채취 33
3) 혈액분리 33
5. 인지 행동학적 지표 분석 34
1) 신물체 탐색 34
2) Y-미로 34
6. 콜린성 신경계(Cholinergic system) 조절 35
1) Acetylcholine(ACh) 함량 35
2) Acetylcholinesterase(AChE) 활성 35
3) Choline acetyl transferase(ChAT) 활성 36
4) BDNF 및 p-CREB 단백질 발현 측정 37
7. β-Amyloid 형성 39
1) β-Secretase(BACE1) 활성 39
2) Amyloid beta 40 함량 40
3) Amyloid beta 42 함량 41
8. DNA 손상 보호(Comet assay) 42
1) 뇌 조직 DNA 손상 보호 42
2) 백혈구 DNA 손상 보호 43
9. 혈액의 항산화 효소 분석 44
1) 혈장 내 활성산소 흡수능력(Oxygen radical absorbance capacity; ORAC) 측정 44
2) 적혈구 내 superoxide dismutase(SOD) 효소 측정 44
3) 적혈구 내 glutathione-peroxidase(GSH-Px) 효소 측정 45
4) 적혈구 내 catalase(CAT) 효소 측정 45
10. 통계 분석 46
Ⅲ. 연구결과 47
1. 산화스트레스에 대한 신경세포 보호 효과 47
2. 체중, 식이 섭취량 및 장기 무게 49
3. 인지 행동학적 지표 52
1) 신물질 탐색 52
2) Y-미로 54
4. 콜린성 신경계(Cholinergic system) 조절 효과 56
1) Acetylcholine(ACh) 함량 56
2) Acetylcholinesterase(AChE) 활성 58
3) Choline acetyl transferase(ChAT) 활성 60
4) BDNF 및 p-CREB 단백질 발현 62
5. β-Amyloid 형성 65
1) β-Secretase(BACE1) 활성 65
2) Amyloid beta 40 및 42 함량 67
6. DNA 손상 보호(Comet assay) 효과 70
1) 뇌 조직 DNA 손상 보호 효과 70
2) 백혈구 DNA 손상 보호 효과 72
7. 혈액의 항산화 효소 활성 74
1) 혈장 내 ORAC 활성 74
2) 적혈구 내 SOD, GSH-Px, CAT 효소 활성 74
Ⅳ. 고찰 및 결론 77
References 83
ABSTRACT 95
Table 1. Dementia mortality by age 14
Table 2. Daily intake of the subjects 31
Table 3. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on weight gain and food intake 50
Table 4. Effect of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on the relative organ weight in scopolamine treated mice 51
Table 5. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on plasma oxygen radical absorbance capacity(ORAC) and erythrocyte antioxidant enzyme in scopolamine-induced memory impaired mice 76
Fig. 1. Mechanisms involved in the pathogenesis of cholinergic dysfunction 17
Fig. 2. Mechanisms through PKA/CREB/BDNF and PI3K/AKT/CREB/BDNF pathways 20
Fig. 3. Mechanisms involved in the pathogenesis of tau protein 21
Fig. 4. Mechanisms involved in the pathogenesis of oxidative stress 23
Fig. 5. Experimental design of animals. 32
Fig. 6. Effect of hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on H₂O₂ induced SK-N-SH cell death 48
Fig. 7. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on recognition index(A) and object... 53
Fig. 8. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on Y-maze test in scopolamine-induced... 55
Fig. 9. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on ACh contents in mice hippocampus... 57
Fig. 10. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on AChE activity in mice hippocampus... 59
Fig. 11. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on ChAT activity in mice hippocampus... 61
Fig. 12. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on western blot analysis protein level... 63
Fig. 13. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on western blot analysis protein level... 64
Fig. 14. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on β-secretase in mice hippocampus... 66
Fig. 15. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on β-amyloid 40 in mice hippocampus... 68
Fig. 16. Effects of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on β-amyloid 42 in mice hippocampus... 69
Fig. 17. Antigenotoxic effect of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on DNA damage of... 71
Fig. 18. Antigenotoxic effect of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 on DNA damage of... 73
Fig. 19. Schematic diagram showing the effect of two-year-old hydroponic-cultured ginseng fermented with Lactococcus lactis KC24 in Alzheimer's disease 82