Title Page
Contents
ABSTRACT 9
Ⅰ. Introduction 11
1.1. Senescence 11
1.2. Ephrin and Eph receptor 14
1.3. Ephrin and Eph receptor in Drosophila 17
1.4. Alzheimer disease 17
1.5. Drosophila model of Alzheimer disease 19
1.6. Drosophila glial cells 19
1.7. Purpose of this study 22
Ⅱ. Materials and Methods 23
2.1. Drosophila strains 23
2.2. Preparation of RNA and RT-qPCR 23
2.3. Longevity assay 24
2.4. Immunohistochemistry 24
2.5. Histology 25
2.6. Evaluation of behavior 26
2.7. Gene ontology data analysis 26
2.8. Statistics 26
Ⅲ. Results 27
3.1. Screening of glial secretome genes that affect lifespan 27
3.2. Gene ontology analysis of screened genes 27
3.3. Glial-specific Ephrin/Eph knockdown reduces lifespan 28
3.4. Ephrin and Eph affect Aβ pathology 29
3.5. Glial-specific Ephrin/Eph knockdown does not affect Drosophila brain development 29
3.6. Glial-specific Ephrin/Eph knockdown neuronal cell death in the AD model brains 30
3.7. Glial-specific Ephrin/Eph knockdown increases Aβ accumulation in neurons in the AD model brains 31
3.8. Glial-specific Ephrin/Eph knockdown increases neuronal protein aggregation in the AD model brains 31
3.9. Glial-specific Ephrin/Eph knockdown alters behavior of Drosophila model of AD 32
Ⅳ. Discussion 47
References 51
Abstract (in Korean) 64
Figure 1. Function of senescence in the cell. 13
Figure 2. Structure of Ephrin and Eph. 16
Figure 3. Glia cells of Drosophila CNS. 21
Figure 4. Methods for screening age-related glial secretome gene. 33
Figure 5. Results of age-associated glial secretome gene screening. 34
Figure 6. Biological pathways associated with senescence-associated glial secretome genes. 35
Figure 7. The function of glial Ephrin and Eph in systemic aging in Drosophila. 36
Figure 8. Ephrin and Eph expression during aging in Drosophila glia. 37
Figure 9. Ephrin and Eph mRNA levels in the presence of Aβ. 38
Figure 10. Dual binary gene expression system in the Drosophila. 39
Figure 11. Ephrin and Eph knockdown does not affect glia cell number in the brains of AD model. 40
Figure 12. Ephrin and Eph knockdown does not affect neurons in the brain of AD model. 41
Figure 13. Glia-specific Ephrin and Eph knockdown increases neuronal death in the brain of AD model. 42
Figure 14. Glia-specific Ephrin and Eph knockdown increases Aβ42 aggregates in the brain. 43
Figure 15. Glia-specific Ephrin and Eph knockdown increases the proteostasis impairment during aging in the presence of Aβ. 44
Figure 16. Function of Ephrin and Eph in locomotor activity and circadian rhythm in Drosophila. 45
Figure 17. Function of Ephrin and Eph in the sleep of Drosophila. 46