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22대 대한민국 국회 국회정보길라잡이 국회의원검색
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Title Page

Abstract

Contents

List of Abbreviations 11

Introduction 13

1. Age-related neurodegenerative disorders : Alzheimer’s disease 13

2. Acetylcholine metabolism and memory impairments 14

3. b-Amyloid and neuronal damages 15

4. Traditional herbal medicines and their constituents for the prevention and/or treatment of AD 18

5. Potential new molecular targets for the prevention and/or treatment of AD 20

6. Statement of purpose 22

Materials and Methods 23

1. Materials 23

2. Animals and drug administration 23

3. Y-maze task 24

4. Morris water-maze task 24

5. Passive avoidance task 25

6. Contextual fear conditioning task 26

7. Cell culture 27

8. Measurement of cell viability 27

9. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling : TUNEL staining 28

10. Measurements of the mitochondrial membrane potential (ΔY) : Tetramethyl-rhodamine ethyl ester (TMRE) staining 28

11. Measurement of caspase-3 activity 29

12. Western blot analysis 29

13. Measurement of reactive oxygen species (ROS) : 2´7´-dichlorofluroscein-diacetate (DCF-DA) staining 30

14. Measurement of peroxynitrite generation : Dihydrhodamine 123 staining 31

15. Assessment of lipid peroxidation 31

16. Mesurement of intracellular GSH levels 32

17. Reverse transcription-polymerase chain reaction : RT-PCR 32

18. Immunocytochemistry 34

19. Luciferase assay 34

20. Statistical analysis 35

Results 36

1. Effect of ginger extracts on the scopolamine-induced learning memory impairments in C57BL/6 mice 36

2. Effect of [6]-gingerol on the cognitive dysfunction induced by scopolamine in C57BL/6 mice 41

3. Protective effect of [6]-gingerol on Ab-induced cytotoxicity and apoptosis in SH-SY5Y cells 46

4. Protective effect of [6]-gingerol on Ab-induced oxidative damages 58

5. [6]-Gingerol-induced activation of Nrf2 and its target genes 63

Discussion 76

References 83

국문초록 96

List of Figures

Fig. 1. Schematic diagram of Ab-induced oxidative and/or nitrosative neuronal cell death via apoptosis 17

Fig. 2. Representative chemical structures of major components of ginger 19

Fig. 3. Memory enhancing effects of ginger extracts in Y-maze task 37

Fig. 4. Memory enhancing effects of ginger extracts in Morris water-maze task 39

Fig. 5. Protective effect of [6]-gingerol on the learning and memory deficit caused by scopolamine in Y-maze task 42

Fig. 6. Protective effect of [6]-gingerol on the learning and memory deficit caused by scopolamine in Morris water-maze task 44

Fig. 7. Protective effect of [6]-gingerol on the learning and memory deficit caused by scopolamine in passive avoidance task 47

Fig. 8. Protective effect of [6]-gingerol on the learning and memory deficit caused by scopolamine in contextual fear conditioning task 49

Fig. 9. Protective effect of [6]-gingerol on the Ab25-35-induced cytotoxicity and apoptotic cell death 51

Fig. 10. Inhibitory effect of [6]-gingerol on the Ab25-35-induced dissipation of mitochondrial potential 54

Fig. 11. Inhibitory effect of [6]-gingerol on the Ab25-35-induced pro-apototic signals 56

Fig. 12. Inhibitory effect of [6]-gingerol on the Ab25-35-induced intracellular accumulation of ROS 59

Fig. 13. Inhibitory effect of [6]-gingerol on the Ab25-35-induced intracellular accumulation of RNS 61

Fig. 14. Protective effect of [6]-gingerol on the Ab25-35-induced oxidative damages 64

Fig. 15. Effects of [6]-gingerol on the mRNA and protein expression of GCL and HO-1 66

Fig. 16. Effects of [6]-gingerol on the mRNA expression of other antioxidant enzymes 69

Fig. 17. [6]-gingerol-induced activation of Nrf2 70

Fig. 18. Effect of pharmacological inhibior PI3K on the [6]-gingerol-induced HO-1 expression 72

Fig. 19. Possible molecular mechanisms for the neuroprotective and memory enhancing effects of [6]-gingerol 75

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