표제지
목차
LIST OF ABBREVIATION 14
ABSTRACT 15
Ⅰ. 서론 17
Ⅱ. 연구사 19
A. Attention deficit hyperactivity disorder(ADHD) 19
1. ADHD 진단 19
2. ADHD 원인 20
3. ADHD 동물모델 22
B. ADHD와 Omega-3 지방산 22
1. 식물성 Omega-3 지방산 22
2. 임신 중 Omega-3 지방산 섭취 24
C. 염증성 사이토카인과 세로토닌 26
1. ADHD와 염증성 사이토카인 26
2. ADHD와 세로토닌 27
D. 신경영양인자 33
1. ADHD와 BDNF 33
2. Omega-3 지방산과 BDNF 신호전달 경로 36
Ⅲ. 재료 및 방법 38
A. 동물실험 38
1. 실험 동물 사육 38
2. 식이 조성 44
B. 행동 실험 47
1. Open field test 47
2. Marble burying test 49
3. Elevated plus maze test (EPM) 51
4. Y-maze test 53
5. Forced swimming test 55
C. 시료 채취 및 분석 57
1. 희생 및 채혈 방법 57
2. 해마 조직 분리 및 전처리 57
3. ELISA 분석 60
4. Western blot 분석 63
D. 자료 처리 및 통계 66
Ⅳ. 결과 67
A. 자손 쥐의 체중 변화 67
B. 자손 쥐의 행동학적 변화 69
1. OFT 결과 69
2. MBT 결과 74
3. EPM 결과 77
4. Y-maze test 결과 82
5. FST 결과 85
C. 자손 쥐의 혈중 항목 변화 92
1. 그룹 간 inflammatory cyokines 수준 비교 92
2. 그룹 간 serotonin 수준 비교 95
D. 자손 쥐의 조직 무게 및 단백질 발현 결과 97
1. 조직 무게 비교 97
2. 해마의 BDNF 및 TrkB 단백질 발현 및 정량 분석 99
3. 해마의 AKT, ERK, CREB 단백질 발현 및 정량분석 101
Ⅴ. 고찰 103
Ⅵ. 결론 113
참고문헌 116
Table 1. Details of experimental animal groups 40
Table 2. Classification of rat offspring in groups 41
Table 3. Nutrient component of the experimental diet 45
Table 4. Comparison of omega-3 PUFA content in plant-based oils 46
Table 5. ELISA kit list 62
Table 6. List of Western blot primary antibody 65
Figure 1. Central serotonergic pathways 29
Figure 2. Micronutrient regulation of the serotonin pathway 31
Figure 3. EPA and DHA improve serotonin synthesis. 32
Figure 4. Signaling pathway of BDNF. 35
Figure 5. Interaction between omega-3 fatty acids and BDNF. 37
Figure 6. Overall research process 42
Figure 7. Maternal rat and rat offspring(left: rat offspring at birth, right: rat offspring while lactation) 43
Figure 8. Open field test. 48
Figure 9. Marble burying test 50
Figure 10. Elevated plus maze test 52
Figure 11. Y-maze test. 54
Figure 12. Forced swimming test. 56
Figure 13. Hippocampal Isolation Process. 59
Figure 14. Comparison of body weights of rat offspring from 1 to 7 weeks after birth(top: male group, bottom: female group).... 68
Figure 15. Difference in the ratio of distance moved(cm) among rat offspring groups(top: male group, bottom: female group).... 70
Figure 16. Representative pathways of each group in the OFT. 71
Figure 17. Difference in the ratio of velocity mean(cm/s) among rat offspring groups(top: male group, bottom: female group).... 73
Figure 18. Difference in the ratio of buried marbles(n) among rat offspring groups(top: male group, bottom: female group).... 75
Figure 19. Representative picture of each group in the MBT. 76
Figure 20. Difference in the ratio of close arm(s) among rat offspring groups(top: male group, bottom: female group).... 78
Figure 21. Representative picture of each group in the EPM. 79
Figure 22. Difference in the ratio of open arm(s) among rat offspring groups(top: male group, bottom: female group).... 81
Figure 23. Difference in the ratio of Spontaneous alteration(%) among rat offspring groups(top: male group, bottom: female group).... 83
Figure 24. Representative pathways of each group in the YMT. 84
Figure 25. Difference in the ratio of immobility time(s) among rat offspring groups(top: male group, bottom: female group).... 86
Figure 26. Representative picture of each group in the FST. 87
Figure 27. Difference in the ratio of climbing time(s) among rat offspring groups(top: male group, bottom: female group).... 89
Figure 28. Difference in the ratio of swimming time(s) among rat offspring groups(top: male group, bottom: female group).... 91
Figure 29. Expression levels of IL-1beta, IL-6, and TNF-αlpha(pg/ml) in the serum of rat offspring groups(left: male group, right: female group).... 94
Figure 30. Expression levels of serotonin(%) in the serum of rat offspring groups(left: male group, right: female group).... 96
Figure 31. Tissue weight comparison among rat offspring groups(left: male group, right: female group).... 98
Figure 32. BDNF and TrkB protein expression in the hippocampus of rat offspring groups(left: male group, right: female group)... 100
Figure 33. AKT, ERK, and CREB protein expression in the hippocampus of rat offspring groups(left: male group, right: female group)... 102