臺灣博碩士論文加值系統

TABLE OF CONTENTS

中文摘要…………………………………………………………...……..i
ABSTRACT...……………………………………………………..……iii
TABLE OF CONTENTS……………………………………...….…….v
FIGURE………………………………………………………………..viii
TABLE………………………………………………………………….xii
Chapter 1. BACKGROUND AND SIGNIFICANCE…………...…….1
1.1 Human angiostrongyliasis……..……………………………….…1
1.2 Clinical Manifestations and Pathology………………..……….…2
1.3 Changes in Animal Behavior Caused by Parasitic Infections and Other Pathogens……………..…………………………………....4
1.4 Animal Model for This Study…………..…………………….…..8
1.5 Evaluation on Factors Associated with the Cognitive Deficits……………..………………………………………...….11
1.5.1 Learning and Memory Test………………………...…...…11
1.5.2 Neuronal Death…………...…………………………….....12
1.5.3 Synaptic integrity………………...…………………….….14
Chapter 2. SPECIFIC AIMS………………….…………………...….16
Chapter 3. EXPERIMENTAL DESIGNS AND RATIONALE….…18
Chapter 4. MATERIALS AND METHODS…….…………………...20
4.1 Establishment and Maintenance of the Life Cycle of A. cantonensis……..…………………………………………….….20
4.2 Experimental Animals………………………………..……..…..21
4.3 Experimental Infection………………..…………………..…….21
4.4 Chemotherapy...………...…………………………………...…..21
4.5 Survival rates…………………………..………………………..22
4.6 Y-Maze Test………………………..……………………….…..22
4.7 Morris Water Maze Test……………………………..….………23
4.8 Novel Object Recognition Task………………………..………..24
4.9 Collection of Blood and Brain Specimens…………..……….….25
4.10 Preparation of Sera………………………………………….….25
4.11 Brain Sections for Pathological Analysis…………..…….……25
4.12 Brain Regions for Western Blotting…………………………...26
4.13 Golgi Staining……………………………………………….…26
4.14 Western Blotting…………………………………………….....27
4.15 Immunochemical Staining……………………………………..27
4.16 Enzyme-Linked Immunosorbent Assay……………………..…28
4.17 Hematoxylin and Eosin Staining…………………………..…..28
4.18 Histopathological Examination………………………………...29
4.19 Sholl analysis…………………………………………………..29
4.20 TUNEL Assay…………………………………………...……..30
4.21 Statistical Analysis…………………………………………..…30
Chapter 5. RESULTS……………………….……………………...….31
Chapter 6. DISCUSSION……….………………………………….….38
REFERENCES…………………………………………………………51
FIGURES AND TABLES………………………………………..……67
ABBREVIATIONS…………………………………………………….94
APPENDICES………………………………………………………….96
LIST OF PUBLICATIONS………………………………..….……..100

 
FIGURES

Figure. 1. Life cycle of Angiostrongylus cantonensis…………….……68
Figure. 2. Evaluation of spatial learning and memory of C57BL/6 mice before and after A. cantonensis infection by Morris water maze……………………………………………………..…..69
Figure 3. Evaluation of spatial memory of C57BL/6 mice before and after A. cantonensis infection by NOR task……………..….70
Figure 4. Evaluation of spatial working memory of C57BL/6 mice before and after A. cantonensis infection by Y maze………………71
Figure. 5. Evaluation of spatial learning and memory of infected C57BL/6 mice before and after treatment by Morris water maze……………………………………………………...….72
Figure. 6. Induction of dendrite damages in CA1 pyramidal neurons in A. cantonensis infected mice detected by Golgi staining……....73
Figure. 7. Induction of dendritic spines damages in CA1 pyramidal neurons in A. cantonensis infected mice detected by Golgi staining……………………………………………….……..74
Figure. 8. Induction of dendrite damages in CA1 pyramidal neurons in A. cantonensis infected mice before and after treatment detected by Golgi staining……………………………………...……..75
Figure 9. Changes in the level of PSD95 expression in hippocampus of mice infected with A. cantonensis detected by immunohistochemistry…………………………………...…76
Figure. 10. Changes in the level of synaptophysin expression in hippocampus of mice infected with A. cantonensis detected by immunohistochemistry………………………………...……77
Figure. 11. Changes in the level of NeuN expression in hippocampus of mice infected with A. cantonensis detected by immunohistochemistry………………………………...……78
Figure. 12. Changes in the level of PSD95, synaptophysin and NeuN expression in hippocampus of mice infected with A. cantonensis detected by Western blotting…………………………………………………...…79
Figure. 13. Changes in the level of PSD95, synaptophysin and NeuN expression in prefrontal cortex of mice infected with A. cantonensis detected by Western blotting…………………..80
Figure. 14. Changes in the level of PSD95, synaptophysin and NeuN expression in hippocampus of mice infected with A. cantonensis before and after treatment detected by Western blotting…………………………………………………..…..81
Figure. 15. Changes in the level of PSD95, synaptophysin and NeuN expression in prefrontal cortex of mice infected with A. cantonensis before and after treatment detected by Western blotting…………………………………………….……...…82
Figure. 16. Survival rates of infected mice………………………….….83
Figure. 17. Pathological changes in brain section of infected mice….....84
Figure. 18. Pathological changes in brain section of infected mice before and after treatment……………………………………….….85
Figure. 19. Presence of larvae in different section of brain………...…..86
Figure. 20. Recovery rate and length of larvae in the brain of infected mice at different time points…………………………….…..87
Figure. 21. Expression of cell death-related proteins in the brain of C57BL/6 mice infected with A. cantonensis………………..88
Figure. 22. Expression of cell death-related proteins in the brain of C57BL/6 mice infected with A. cantonensis before and after treatment………………………………………………...…..89
Figure. 23. Fluorometric in situ cell death detection (TUNEL staining)……………………………………………………..90
Figure. 24. Peripheral immunoglobulin expressions in C57BL/6 mice infected with A. cantonensis……………………………...…91
Figure. 25. Synaptic loss and progression in mice infected with Angiostrongylus cantonensis in the early stage……………..92
Supplementary Figure. 1. Functional regions of the mouse brain for Western Blotting…………………………………………….93

 
TABLE

Table. 1. Correlation between occurrence of eosinophilic meningitis and the presence of larvae in meningitis in brain sections of SD rats and ICR mice infected with different numbers of third-stage larvae (L3) of Angiostrongylus cantonensis………………..….67

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