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施万细胞通过隧道纳米管和胰岛素样生长因子-1促进周围神经再生的机制研究

ABSTRACT第6-8页
中文摘要第9-12页
ABBREVIATIONS第12-14页
CHARPTER Ⅰ A BRIEF REVIEW OF REGENERATIVE MICROENVIRONMENT AND CELL COMMUNICATIONDURING PERIPHERAL NERVE REGENERATION第14-41页
    1.1. INTRODUCTION第15-16页
    1.2. TNT MORPHOLOGY AND FUNCTION第16-24页
        1.2.1. TNT Mediated Cargo Transfer第17-18页
        1.2.2. TNTs in Stem Cells第18-19页
        1.2.3. TNTs in Nerve Tissue Cells第19-20页
        1.2.4. TNTs in Immune Cells第20-21页
        1.2.5. TNTs and Cancer第21-22页
        1.2.6. Mitochondrial Transfer by TNTs第22-23页
        1.2.7. Mechanisms of TNTs formation第23-24页
    1.3. INSULIN-LIKE GROWTH FACTOR-1(IGF-1)/INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR(IGF-1R)SIGNALING IN PNI第24-32页
        1.3.1. IGF-1 Signaling第26-28页
        1.3.2. Effects of IGF-1 on Regenerating Axons and SCs第28-29页
        1.3.3. Regulation of IGF-1 Signaling by MicroRNAs第29-31页
        1.3.4. Therapeutic Targeting of MiRNAs Involved in The IGF-1 Signaling Pathway第31-32页
    1.4. OUTLOOK ON REGENERATIVE MICROENVIRONMENT AND PERIPHERAL NERVE REGENERATION第32-33页
    REFERENCE第33-41页
CHARPTER Ⅱ RAB8A/RAB11A REGULATE INTERCELLULAR COMMUNICATIONS BETWEEN NEURALCELLS VIA TUNNELING NANOTUBES第41-70页
    2.1. Introduction第42-43页
    2.2. Materials and Methods第43-49页
        2.2.1. Primary SCs culture and oligonucleotide transfection第43-44页
        2.2.2. Time-lapse imaging of live samples第44页
        2.2.3. Scanning electron microscopy第44-45页
        2.2.4. Quantitative real-time PCR第45页
        2.2.5. Western Blot Analysis第45页
        2.2.6. Sciatic nerve transection第45-46页
        2.2.7. Immunocytochemistry第46页
        2.2.8. Confocal Microscopy第46页
        2.2.9. TNT quantification第46-47页
        2.2.10. Evaluation of cell apoptosis by flow cytometry analysis第47页
        2.2.11. TUNEL staining第47页
        2.2.12. Wound healing assay of primary SCs in vitro第47-48页
        2.2.13. Enzyme-linked immunosorbent assay (ELISA)第48页
        2.2.14. Co-culture of DRG neurons and SCs第48-49页
        2.2.15. Statistical analysis第49页
    2.3. RESULTS第49-62页
        2.3.1. TNTs between SCs and their properties第49-51页
        2.3.2. TNTs facilitate intercellular transfer of lipophilic cytosolic components as well asproteins, mitochondria vesicles between SCs第51-53页
        2.3.3. Newly-synthesized RNA is transferred from SCs to axons after sciatic nerve transectionvia TNTs第53-55页
        2.3.4. Rab8a and Rab 11 a affect the formation of TNTs第55-57页
        2.3.5. Endogenous Rab8a/ Rabl la are necessary for formation and function of TNTs第57-59页
        2.3.6. Knockdown of Rab8a/Rablla promote SCs apoptosis and inhibit migration viasuppression of TNTs formation第59-60页
        2.3.7. Rab8a/ Rab11a may affect neurotrophic factors transport and outgrowth of DRG neuronsneurites co-cultured with SCs via TNTs第60-62页
    2.4. DISCUSSION第62-66页
    2.5. SUMMARY AND PROSPECTIVE VIEW第66页
    Reference第66-70页
CHARPTER Ⅲ MIR-129 CONTROLS AXONAL REGENERATION VIA REGULATING INSULIN-LIKE GROWTHFACTOR 1 IN PERIPHERAL NERVE INJURY第70-97页
    3.1. INTRODUCTION第71-72页
    3.2. MATERIALS AND METHODS第72-77页
        3.2.1. Animals and tissue preparation第72-73页
        3.2.2. Tissue immunohistochemistry第73页
        3.2.3. DRG neuron culture第73-74页
        3.2.4. Primary culture of SCs and cell transfection第74页
        3.2.5. Luciferase reporter assay第74-75页
        3.2.6. Quantitative real-time RT-PCR (qRT-PCR)第75-76页
        3.2.7. Western blot analysis第76页
        3.2.8. ELISA第76页
        3.2.9. Cell proliferation assay第76-77页
        3.2.10. Cell migration assay第77页
        3.2.11. Co-culture of DRG neurons and SCs第77页
        3.2.12. Statistical analysis第77页
    3.3. RESULTS第77-90页
        3.3.1. Temporal changes of IGF-1 expression following sciatic nerve injury第78-80页
        3.3.2. miR-129 negatively regulated IGF-1 by directly targeting its 3'-UTR第80-82页
        3.3.3. miR-129/IGF-1 axis regulates neurite outgrowth from DRG neurons第82-84页
        3.3.4. miR-129 inhibited IGF-1 secretion of SCs第84-85页
        3.3.5. miR-129 suppressed SCs proliferation and migration第85-88页
        3.3.6. Effects of miR-129/IGF-1/IGF-1R pathway on neurite outgrowth in co-culture system ofDRG neurons and SCs第88-90页
    3.4. DISCUSSION第90-92页
    3.5. SUMMARY AND PROSPECTIVE VIEW第92-94页
    Reference第94-97页
ACKNOWLEDGEMENTS第97-98页
PUBLICATIONS第98-100页

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