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題名 在腎上腺摘除模式下觀察微小膠細胞與成體神經前驅細胞之間的關係
Microglia regulation of adult neural progenitor cells
作者 蔡欣學
貢獻者 賴桂珍
蔡欣學
關鍵詞 微小膠細胞
日期 2016
上傳時間 2-Sep-2016 00:14:47 (UTC+8)
摘要 微小膠細胞(microglia)為中樞神經系統中主要免疫功能的神經膠細胞，並且具有吞噬的功能用來移除生病或邁向死亡的細胞。但是近年來越來越多實驗發現微小膠細胞也會調控神經細胞的增生以及分化，甚至可能與調控神經新生有關係。
在腎上腺摘除(ADX)之後發現到齒狀迴(dentate gyrus)中的DGCs死亡以及activated microlgia數量增加，而且這些microglia與NPCs培養後會影響NPCs的分化，因此我們想要利用此模式進一步來了解同樣在hippocampus中的cornus ammonis(CA)以及掌管我們認知行為的PFC腦區在腎上腺摘除之後的microglia否會影響NPCs。實驗結果顯示在ADX後microglia與NPCs共養後，會影響NPCs的cell number以及neurite length。而在CA區取出的ADX microglia-condition medium培養NPCs後發現到會減少NPCs的cell number。從以上可以得知在ADX後的microglia的確改變了自身功能進而影響到了NPCs的分化以及生長，而且來自PFC腦區的Microglia與來自CA腦區的Microglia對於NPCs的影響也不同。
參考文獻 Aarum, J., Sandberg, K., Haeberlein, S. L., & Persson, M. A. (2003). Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci U S A, 100(26), 15983-15988. doi: 10.1073/pnas.2237050100
Aguzzi, A., Barres, B. A., & Bennett, M. L. (2013). Microglia: scapegoat, saboteur, or something else? Science, 339(6116), 156-161. doi: 10.1126/science.1227901
Altman, & Das. (1965). POST-NATAL ORIGIN OF MICRONEURONES IN THE RAT BRAIN.
Battista, D., Ferrari, C. C., Gage, F. H., & Pitossi, F. J. (2006). Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci, 23(1), 83-93. doi: 10.1111/j.1460-9568.2005.04539.x
Bedard, & Parent. (2004). Evidence of newly generated neurons in the human olfactory bulb. Brain Res Dev Brain Res, 151(1-2), 159-168. doi: 10.1016/j.devbrainres.2004.03.021
Choi, S. H., Veeraraghavalu, K., Lazarov, O., Marler, S., Ransohoff, R. M., Ramirez, J. M., & Sisodia, S. S. (2008). Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron, 59(4), 568-580. doi: 10.1016/j.neuron.2008.07.033
Couch, Y., Anthony, D. C., Dolgov, O., Revischin, A., Festoff, B., Santos, A. I., . . . Strekalova, T. (2013). Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain Behav Immun, 29, 136-146. doi: 10.1016/j.bbi.2012.12.017
Cunningham, C. L. M.-C., V.Noctor, S. C. (2013). Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci, 33(10), 4216-4233. doi: 10.1523/JNEUROSCI.3441-12.2013
Eriksson, PERFILIEVA, NORDBORG, BJÖRK-ERIKSSON, PETERSON, ALBORN, & GAGE. (1998). Neurogenesis in the adult human hippocampus.
Herrera, A. J., Espinosa-Oliva, A. M., Carrillo-Jimenez, A., Oliva-Martin, M. J., Garcia-Revilla, J., Garcia-Quintanilla, A., . . . Venero, J. L. (2015). Relevance of chronic stress and the two faces of microglia in Parkinson`s disease. Front Cell Neurosci, 9, 312. doi: 10.3389/fncel.2015.00312
Hinwood, M., Tynan, R. J., Charnley, J. L., Beynon, S. B., Day, T. A., & Walker, F. R. (2013). Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb Cortex, 23(8), 1784-1797. doi: 10.1093/cercor/bhs151
Inokuchi. (2011). Adult neurogenesis and modulation of neural circuit function. Curr Opin Neurobiol, 21(2), 360-364. doi: 10.1016/j.conb.2011.02.006
Kettenmann, Hanisch, Noda, & Verkhratsky. (2011). Physiology of Microglia. Physiol Rev. doi: 10.1152/physrev.00011.2010.-Microglial
Moga, Dempah, & Zhou. (2005). Annexin 7-immunoreactive microglia in the hippocampus of control and adrenalectomized rats. Neurosci Lett, 380(1-2), 42-47. doi: 10.1016/j.neulet.2005.01.022
Morgan, S. C., Taylor, D. L., & Pocock, J. M. (2004). Microglia release activators of neuronal proliferation mediated by activation of mitogen-activated protein kinase, phosphatidylinositol-3-kinase/Akt and delta-Notch signalling cascades. J Neurochem, 90(1), 89-101. doi: 10.1111/j.1471-4159.2004.02461.x
Nichols, N. R., Agolley, D., Zieba, M., & Bye, N. (2005). Glucocorticoid regulation of glial responses during hippocampal neurodegeneration and regeneration. Brain Res Brain Res Rev, 48(2), 287-301. doi: 10.1016/j.brainresrev.2004.12.019
Nimmerjahn, Kirchhoff, & Helmchen. (2005
). Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo. Science,
.
Paolicelli, R. C. I. (2011). Synaptic pruning by microglia is essential for normal brain development. Science.
Postigo, Werf, Korf, & Krugers. (1998). Altered expression of the cell cycle regulatory protein cyclin D1 in the rat dentate gyrus after adrenalectomy-induced granular cell loss. Neurosci Lett.
Praag, Christie, Sejnowski, & Gage. (1999). Running enhances neurogenesis, learning, and long-term potentiation in mice.
Sierra, A., Encinas, J. M., Deudero, J. J., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., . . . Maletic-Savatic, M. (2010). Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell, 7(4), 483-495. doi: 10.1016/j.stem.2010.08.014
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F. (2012). Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J Neurosci, 32(19), 6435-6443. doi: 10.1523/JNEUROSCI.5925-11.2012
Walton, N. M., Sutter, B. M., Laywell, E. D., Levkoff, L. H., Kearns, S. M., Marshall, G. P., 2nd, . . . Steindler, D. A. (2006). Microglia instruct subventricular zone neurogenesis. Glia, 54(8), 815-825. doi: 10.1002/glia.20419
Ziv, Y., & Schwartz, M. (2008). Immune-based regulation of adult neurogenesis: implications for learning and memory. Brain Behav Immun, 22(2), 167-176. doi: 10.1016/j.bbi.2007.08.006
描述 碩士
國立政治大學
神經科學研究所
100754009
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0100754009
資料類型 thesis
dc.contributor.advisor 賴桂珍zh_TW
dc.contributor.author (Authors) 蔡欣學zh_TW
dc.creator (作者) 蔡欣學zh_TW
dc.date (日期) 2016en_US
dc.date.accessioned 2-Sep-2016 00:14:47 (UTC+8)-
dc.date.available 2-Sep-2016 00:14:47 (UTC+8)-
dc.date.issued (上傳時間) 2-Sep-2016 00:14:47 (UTC+8)-
dc.identifier (Other Identifiers) G0100754009en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/101131-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 神經科學研究所zh_TW
dc.description (描述) 100754009zh_TW
dc.description.abstract (摘要) 微小膠細胞(microglia)為中樞神經系統中主要免疫功能的神經膠細胞，並且具有吞噬的功能用來移除生病或邁向死亡的細胞。但是近年來越來越多實驗發現微小膠細胞也會調控神經細胞的增生以及分化，甚至可能與調控神經新生有關係。
在腎上腺摘除(ADX)之後發現到齒狀迴(dentate gyrus)中的DGCs死亡以及activated microlgia數量增加，而且這些microglia與NPCs培養後會影響NPCs的分化，因此我們想要利用此模式進一步來了解同樣在hippocampus中的cornus ammonis(CA)以及掌管我們認知行為的PFC腦區在腎上腺摘除之後的microglia否會影響NPCs。實驗結果顯示在ADX後microglia與NPCs共養後，會影響NPCs的cell number以及neurite length。而在CA區取出的ADX microglia-condition medium培養NPCs後發現到會減少NPCs的cell number。從以上可以得知在ADX後的microglia的確改變了自身功能進而影響到了NPCs的分化以及生長，而且來自PFC腦區的Microglia與來自CA腦區的Microglia對於NPCs的影響也不同。		zh_TW
dc.description.tableofcontents 中文摘要--------------------------------------------------1
英文摘要--------------------------------------------------2
縮寫表----------------------------------------------------3
第一章 緒論-----------------------------------------------7
一、 成年神經新生(Adult neurogenesis) --------------------7
二、 微小膠細胞(Microglia) -------------------------------8
三、 Microglia 與成體神經新生-----------------------------9
四、 Microglia與腎上線移除手術(Adrenalectomy，ADX)------11
五、 研究動機--------------------------------------------12
六、 研究目標--------------------------------------------13
第二章 材料方法------------------------------------------14
一、 實驗流程--------------------------------------------14
二、 實驗動物--------------------------------------------14
三、 腎上腺移除手術(Adrenalectomy，ADX) -----------------14
6
四、 初代細胞培養(primary cell culture) -----------------16
第三章 結果----------------------------------------------26
一、 Adrenalectomy(ADX)後 hippocampus CA 腦區 and PFC 腦區
的microglia 與 DG 腦區的 NPCs 共同培養的觀察--------26
二、 Microglia conditioned medium對DG NPCs的影響-------38
三、 Medium與coculture比較-----------------------------49
第四章 討論----------------------------------------------51
參考文獻-------------------------------------------------55		zh_TW
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0100754009en_US
dc.subject (關鍵詞) 微小膠細胞zh_TW
dc.title (題名) 在腎上腺摘除模式下觀察微小膠細胞與成體神經前驅細胞之間的關係zh_TW
dc.title (題名) Microglia regulation of adult neural progenitor cellsen_US
dc.type (資料類型) thesisen_US
dc.relation.reference (參考文獻) Aarum, J., Sandberg, K., Haeberlein, S. L., & Persson, M. A. (2003). Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci U S A, 100(26), 15983-15988. doi: 10.1073/pnas.2237050100
Aguzzi, A., Barres, B. A., & Bennett, M. L. (2013). Microglia: scapegoat, saboteur, or something else? Science, 339(6116), 156-161. doi: 10.1126/science.1227901
Altman, & Das. (1965). POST-NATAL ORIGIN OF MICRONEURONES IN THE RAT BRAIN.
Battista, D., Ferrari, C. C., Gage, F. H., & Pitossi, F. J. (2006). Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci, 23(1), 83-93. doi: 10.1111/j.1460-9568.2005.04539.x
Bedard, & Parent. (2004). Evidence of newly generated neurons in the human olfactory bulb. Brain Res Dev Brain Res, 151(1-2), 159-168. doi: 10.1016/j.devbrainres.2004.03.021
Choi, S. H., Veeraraghavalu, K., Lazarov, O., Marler, S., Ransohoff, R. M., Ramirez, J. M., & Sisodia, S. S. (2008). Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron, 59(4), 568-580. doi: 10.1016/j.neuron.2008.07.033
Couch, Y., Anthony, D. C., Dolgov, O., Revischin, A., Festoff, B., Santos, A. I., . . . Strekalova, T. (2013). Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain Behav Immun, 29, 136-146. doi: 10.1016/j.bbi.2012.12.017
Cunningham, C. L. M.-C., V.Noctor, S. C. (2013). Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci, 33(10), 4216-4233. doi: 10.1523/JNEUROSCI.3441-12.2013
Eriksson, PERFILIEVA, NORDBORG, BJÖRK-ERIKSSON, PETERSON, ALBORN, & GAGE. (1998). Neurogenesis in the adult human hippocampus.
Herrera, A. J., Espinosa-Oliva, A. M., Carrillo-Jimenez, A., Oliva-Martin, M. J., Garcia-Revilla, J., Garcia-Quintanilla, A., . . . Venero, J. L. (2015). Relevance of chronic stress and the two faces of microglia in Parkinson`s disease. Front Cell Neurosci, 9, 312. doi: 10.3389/fncel.2015.00312
Hinwood, M., Tynan, R. J., Charnley, J. L., Beynon, S. B., Day, T. A., & Walker, F. R. (2013). Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb Cortex, 23(8), 1784-1797. doi: 10.1093/cercor/bhs151
Inokuchi. (2011). Adult neurogenesis and modulation of neural circuit function. Curr Opin Neurobiol, 21(2), 360-364. doi: 10.1016/j.conb.2011.02.006
Kettenmann, Hanisch, Noda, & Verkhratsky. (2011). Physiology of Microglia. Physiol Rev. doi: 10.1152/physrev.00011.2010.-Microglial
Moga, Dempah, & Zhou. (2005). Annexin 7-immunoreactive microglia in the hippocampus of control and adrenalectomized rats. Neurosci Lett, 380(1-2), 42-47. doi: 10.1016/j.neulet.2005.01.022
Morgan, S. C., Taylor, D. L., & Pocock, J. M. (2004). Microglia release activators of neuronal proliferation mediated by activation of mitogen-activated protein kinase, phosphatidylinositol-3-kinase/Akt and delta-Notch signalling cascades. J Neurochem, 90(1), 89-101. doi: 10.1111/j.1471-4159.2004.02461.x
Nichols, N. R., Agolley, D., Zieba, M., & Bye, N. (2005). Glucocorticoid regulation of glial responses during hippocampal neurodegeneration and regeneration. Brain Res Brain Res Rev, 48(2), 287-301. doi: 10.1016/j.brainresrev.2004.12.019
Nimmerjahn, Kirchhoff, & Helmchen. (2005
). Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo. Science,
.
Paolicelli, R. C. I. (2011). Synaptic pruning by microglia is essential for normal brain development. Science.
Postigo, Werf, Korf, & Krugers. (1998). Altered expression of the cell cycle regulatory protein cyclin D1 in the rat dentate gyrus after adrenalectomy-induced granular cell loss. Neurosci Lett.
Praag, Christie, Sejnowski, & Gage. (1999). Running enhances neurogenesis, learning, and long-term potentiation in mice.
Sierra, A., Encinas, J. M., Deudero, J. J., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., . . . Maletic-Savatic, M. (2010). Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell, 7(4), 483-495. doi: 10.1016/j.stem.2010.08.014
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F. (2012). Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J Neurosci, 32(19), 6435-6443. doi: 10.1523/JNEUROSCI.5925-11.2012
Walton, N. M., Sutter, B. M., Laywell, E. D., Levkoff, L. H., Kearns, S. M., Marshall, G. P., 2nd, . . . Steindler, D. A. (2006). Microglia instruct subventricular zone neurogenesis. Glia, 54(8), 815-825. doi: 10.1002/glia.20419
Ziv, Y., & Schwartz, M. (2008). Immune-based regulation of adult neurogenesis: implications for learning and memory. Brain Behav Immun, 22(2), 167-176. doi: 10.1016/j.bbi.2007.08.006		zh_TW