摘要 | 第8-11页 |
ABSTRACT | 第11-13页 |
Abbreviations | 第14-16页 |
Introduction | 第16-18页 |
PART ONE Literature Review | 第18-40页 |
Chapter 1 Role of Cholesterol in the Brain | 第18-28页 |
1.1 Cholesterol in the Brain | 第18-19页 |
1.2 Cholesterol Synthesis | 第19-20页 |
1.3 Cholesterol Homeostasis | 第20-22页 |
1.4 Cholesterol and Brain Function | 第22-24页 |
References | 第24-28页 |
Chapter 2 Effect of Betaine on Cholesterol Metabolism | 第28-34页 |
2.1 Betaine and Cholesterol Metabolism | 第28页 |
2.2 Epigenetic regulation of Cholesterol Metabolism | 第28-29页 |
2.3 Transgenerational Programming | 第29-32页 |
References | 第32-34页 |
Chapter 3 Betaine and Methionine Metabolic Pathway | 第34-40页 |
3.1 Methionine Cycle | 第34-35页 |
3.2 Betaine and Epigenetic Regulation | 第35页 |
3.3 Regulators of DNA Methylation | 第35-38页 |
References | 第38-40页 |
PART TWO Research Work | 第40-106页 |
Chapter 4 Prenatal Betaine Exposure Modulates Hypothalamic Expression of Cholesterol MetabolicGenes in Cockerels through Modifications of DNA Methylation | 第40-64页 |
4.1 Introduction | 第41-43页 |
4.2 Materials and Methods | 第43-47页 |
4.2.1 Ethics Statement | 第43页 |
4.2.2 Animals and Treatment | 第43-44页 |
4.2.3 Behaviour Test | 第44页 |
4.2.4 Total Cholesterol, Cholesterol Ester and Free Cholesterol Content | 第44-46页 |
4.2.5 Total RNA Isolation and Quantitative Real-Time PCR | 第46页 |
4.2.6 Protein Extraction and Western Blotting | 第46-47页 |
4.2.7 Methylated DNA Immune Precipitation (MeDIP) Analysis | 第47页 |
4.2.8 Statistical Analysis | 第47页 |
4.3 Results | 第47-54页 |
4.3.1 Body Weight, Aggressive Behavior and Hypothalamus Content ofCholesterol | 第47-49页 |
4.3.2 Hypothalamic Expression of Cholesterol Metabolic Genes | 第49-50页 |
4.3.3 Hypothalamic Expression of Betaine Metabolism and Methyl TransferGenes | 第50-51页 |
4.3.4 Hypothalamic Expression of Betaine Metabolism and Methyl TransferGenes | 第51-52页 |
4.3.5 DNA Methylation Status on the Promoter of Modified CholesterolMetabolic Genes | 第52-54页 |
4.4 Discussion | 第54-58页 |
References | 第58-64页 |
Chapter 5 Dietary Betaine Supplementation in Hens Modulates Hypothalamic Expression ofCholesterol Metabolic Genes in F1 Cockerels through Modification of DNA Methylation | 第64-86页 |
5.1 Introduction | 第64-66页 |
5.2 Materials and Methods | 第66-71页 |
5.2.1 Ethics Statement | 第66页 |
5.2.2 Animals and Treatment | 第66-67页 |
5.2.3 Total Cholesterol, Cholesterol Ester, and Free Cholesterol Content | 第67-68页 |
5.2.4 Plasma Concentration of Total Cholesterol,HDL-C,and LDL-C | 第68页 |
5.2.5 Total RNA Isolation and Quantitative Real-Time PCR | 第68-70页 |
5.2.6 Protein Extraction and Western Blotting | 第70页 |
5.2.7 Bisulfite Sequencing PCR (BSP) | 第70-71页 |
5.3 Result | 第71-78页 |
5.3.1 Hypothalamus Content of Cholesterol | 第71页 |
5.3.2 Total cholesterol, HDL-C and LDL-C concentration in the plasma | 第71-72页 |
5.3.3 Hypothalamic Expression of Cholesterol Metabolic Genes/proteins | 第72-73页 |
5.3.4 Hypothalamic Expression of Neuropeptides Genes | 第73-74页 |
5.3.5 Hypothalamic Expression of Betaine Metabolism and Methyl TransferGenes | 第74-75页 |
5.3.6 CpG methylation of SREBP1, SREBP2, and APO-A1 gene promoters inthe hypothalamus | 第75-78页 |
5.4 Discussion | 第78-82页 |
References | 第82-86页 |
Chapter 6 Prenatal betaine exposure in hens modulates hypothalamic expression of cholesterolmetabolic genes in F2 cockerels with modification of promoter DNA methylation | 第86-106页 |
6.1 Introduction | 第87-88页 |
6.2 Materials and Methods | 第88-94页 |
6.2.1 Ethics Statement | 第88-89页 |
6.2.2 Animals and Treatment | 第89-90页 |
6.2.3 Total Cholesterol, Cholesterol Ester and Free Cholesterol Content | 第90页 |
6.2.4 Plasma Concentration of Total Cholesterol,HDL-C,and LDL-C | 第90页 |
6.2.5 Hypothalamus Content of SAM and SAH | 第90-91页 |
6.2.6 Total RNA Isolation and Quantitative Real-Time PCR | 第91-92页 |
6.2.7 Protein Extraction and Western Blotting | 第92-93页 |
6.2.8 Methylated DNA Immune Precipitation (MeDIP) Analysis | 第93-94页 |
6.2.9 Statistical Analysis | 第94页 |
6.3 Result | 第94-100页 |
6.3.1 Body Weight, Plasma Concentration and Hypothalamic Content ofCholesterol | 第94-95页 |
6.3.2 Hypothalamic Expression of Cholesterol Metabolic Genes | 第95-96页 |
6.3.3 Hypothalamic Expression of Neuropeptide Genes | 第96页 |
6.3.4 Hypothalamic SAM and SAH contents and Expression of Methyl TransferGenes | 第96-98页 |
6.3.5 DNA Methylation Status on the Promoter of Modified Genes | 第98-100页 |
6.4 Discussion | 第100-102页 |
References | 第102-106页 |
Conclusion | 第106-108页 |
Innovation | 第108-110页 |
ACKNOWLEDGEMENTS | 第110-112页 |
List of Published, Submitted and under Preparation Papers | 第112页 |