Anti-derpessant activity and its mechanism of creatine and taurine mixture in Drosophila melanogaster and mouse model
Anti-derpessant activity and its mechanism of creatine and taurine mixture in Drosophila melanogaster and mouse model
- 주제(키워드) Creatine , Taurine , Depression , Monoamine , Neurogrowth factor , Hormone , Inflammation
- 발행기관 고려대학교 대학원
- 지도교수 서형주
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위구분 석사
- 학과 대학원 의생명융합과학과
- 세부전공 바이오식의과학전공
- 원문페이지 124 p
- 실제URI http://www.dcollection.net/handler/korea/000000083432
- UCI I804:11009-000000083432
- DOI 10.23186/korea.000000083432.11009.0000824
- 본문언어 영어
- 제출원본 000045978504
초록/요약
This research investigated the antidepressant effect of creatine and taurine mixtures on the behavioral changes and biomarkers in stress-induced depression Drosophila melanogaster and mice model. Following the selection of creatine and taurine mixture in the depression-like state of Drosophila model induced by vibration, the survival rate, food intake, Drosophila activity monitoring (DAM) system, climbing activity and locomotor were measured. The movement of stressed Drosophila was less than that of non-stressed fruit flies. At this time, the movement of fruit flies recovered to the normal level after intake of the creatine/taurine mixed at 1:1–3:1 ratio. In order to determine the mixing amount of creatine and taurine, anti-depressant effect was measured in ICR mice, which was given immobilized stress. The creatine/taurine mixture (7.5/2.5 mg/kg) showed the most significant antidepressant activity in depressed ICR mice. Antidepressant effects were measured by oral administration of fluoxetine (10 mg/kg), creatine (7.5 mg/kg), taurine (2.5 mg/kg), and creatine/taurine mixture (7.5/2.5 mg/kg) in BALB/c mouse model with chronic mild stress for 5 weeks. Chronic mild stress group showed decreased movement and sucrose preference compared to normal group. On the other hand, the group that performed the stress application and the sample administration increased the activity again. In particular, the behavioral patterns and sucrose preference of fluoxetine group and creatine/taurine mixture group were returned to normal group level. The body weight gain and organ weight decreased by stress also recovered to the normal level due to the sample administration. Following sacrifice, catecholamine and serotonin contents in the brain were analyzed using high performance liquid chromatography (HPLC) system. L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine and 5-hydroxytryptamine (5-HT) in the stress control group were significantly lower than those in the normal group. L-DOPA and 5-HT increased again after intake of creatine/taurine mixture. Stress-related hormone and inflammatory factors were significantly increased in the stress control group. However, stress-related hormone and inflammatory factors were significantly decreased in the creatine/taurine mixture group compared to the stress control group. The signaling protein production of brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), phospho-protein kinase B (p-AKT) extracellular-signal-regulated kinase (ERK), phospho-extracellular-signal-regulated kinase (p-ERK), cAMP response element binding protein (CREB), and phospho-cAMP response element binding protein (p-CREB) in brain cells was decreased in the stress group compared to the normal group. Fluoxetine, creatine, and creatine/taurine mixture intake showed the increase of the signaling protein production compared to stress group. In conclusion, creatine and taurine showed anti-depressant effects in mild stress-induced depression models. Especially creatine/taurine mixture showed more significant anti-depressant activity than creatine and taurine alone. This anti-depressant activity is due to the decrease of monoamine content in the brain, stress hormone regulation and inflammatory factors in the brain cell. Administration of creatine/taurine mixture resulted increase of signaling proteins production of BDNF, p-AKT, p-ERK and p-CREB.
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ABSTRACT 4
CONTENTS 7
LIST OF TABLES 11
LIST OF FIGURES 12
LIST OF ABBREVIATIONS 14
INTRODUCTION 17
Chapter 1. 24
I. MATERIALS AND METHODS 25
1.1.1. Chemicals and reagent 25
1.1.2. Drosophila melanogaster stock and rearing condition 25
1.1.3. Vibration stress treatment to Drosophila melanogaster 26
1.1.4. Survival rate study of D. melanogaster 26
1.1.5. Drosophila activity monitoring system 26
1.1.6. Video tracking: open field assay 27
1.1.7. Climbing activity assay 29
1.2.8. Statistical analysis 30
II. RESULTS AND DISCUSSION 33
1.2.1. Effect of creatine and taurine on survival rate under vibration stress 33
1.2.2. Effect of creatine and taurine on behavioral pattern under vibration stress using Drosophila activity monitoring system (DAM) 35
1.2.3. Effect of creatine and taurine on behavioral pattern under vibration stress using video tracking 40
1.2.4. Effect of creatine and taurine on climbing activity under vibration stress 43
Chapter 2. 45
I. MATERIALS AND METHODS 46
2.1.1. Chemicals and reagent 46
2.1.2. Animal 46
2.1.3. Stress treatment 46
2.1.4. Open field test 47
2.1.5. Tail suspension test 47
2.1.6. Statistical analysis 47
II. RESULTS AND DISCUSSION 49
2.2.1. Single sample administration experiment 49
2.2.2. Mixture of sample administration experiment 54
Chapter 3. 61
I. MATERIALS AND METHODS 62
3.1.1. Chemical and reagent 62
3.1.2. Animal 62
3.1.3. Chronic mild stress 62
3.1.4. Open field test 65
3.1.4. Tail suspension test 65
3.1.5. Sucrose preference test 66
3.1.6. Forced swimming test 66
3.1.7. Hormone and cytokine assay using ELISA 67
3.1.8. Catecholamine assay using HPLC 67
3.1.9. mRNA expression assay by qRT-PCR 68
3.1.10. Protein expression level assay by western blotting 69
II. RESULTS AND DISCUSSION 71
3.2.1. Body weight, food intake and organ weight during experiment 71
3.2.2. Effect of a mixture of creatine and taurine on open field test under mild stress-induced depression 75
3.2.3. Effect of a mixture of creatine and taurine on tail suspension test under mild stress-induced depression 79
3.2.4. Effect of a mixture of creatine and taurine on sucrose preference under mild stress-induced depression 83
3.2.5. Effect of a mixture of creatine and taurine on forced swimming test under mild stress-induced depression 86
3.2.6. Effect of a mixture of creatine and taurine on catecholamine and serotonin under mild stress-induced depression 89
3.2.7. Effect of a mixture of creatine and taurine on CRH mRNA expression under mild stress-induced depression 93
3.2.8. Effect of a mixture of creatine and taurine on stress hormone and cytokines under mild stress-induced depression 95
3.2.9. Anti-depressant mechanism of a mixture of creatine and taurine 100
CONCLUSION 108
ABSTRACT IN KOREAN 110
REFERENCE 112
