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研究生: 蕭昊亮
Hsiao, Hao-Liang
論文名稱: 探討成年嗅球神經元新生在雌鼠生殖行為中所扮演的角色
The role of adult olfactory bulb neurogenesis in female mouse reproduction
指導教授: 王慈蔚
Wang, Tsu-Wei
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2015
畢業學年度: 104
語文別: 英文
論文頁數: 44
中文關鍵詞: 成年神經元新生神經幹細胞費洛蒙布魯斯效應生殖行為
英文關鍵詞: Adult neurogenesis, neural stem cell, pheromone, Bruce effect, reproductive behavior
論文種類: 學術論文
相關次數: 點閱:189下載:1
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  • 在成年哺乳類大腦中,位於側腦室旁的側腦室下區與齒狀迴顆粒細胞下區存在有神經幹細胞。在側腦室下區中的神經幹細胞會產生前驅細胞,其會產生神經母細胞。而在此處產生的神經母細胞會沿著rostral migratory stream 移動到嗅球,分化成成熟的神經元,並加入嗅球原有的神經迴路之中。而齒狀迴顆粒細胞下區所產生的神經母細胞,則會往齒狀迴移動,並在成熟後加入神經迴路之中。嗅球分成主嗅球與副嗅球兩個部分。主嗅球主要負責空氣中一般氣味分子的傳遞;而副嗅球主要與費洛蒙訊息的傳遞有關,並會引起動物的先天行為。在先天行為之中,有一個有趣的現象稱為布魯斯效應。布魯斯效應指的是母鼠在懷孕早期因為接觸到其他非伴侶公鼠的費洛蒙後,重新進入動情週期而導致流產。根據實驗室之前的研究發現:公鼠費洛蒙所引起的成年副嗅球神經元新生會因為接觸到不熟悉的公鼠費洛蒙而減少。因此我們假設:成年副嗅球的神經元新生可能與布魯斯效應有關。為了驗證此假說,我們對帶有Nestin-CreER;R26-loxP-STOP-loxP-DTA 的基因轉殖鼠施打tamoxifen,造成側腦室下區的神經幹細胞的死亡,來專一地抑制嗅球的神經元新生。我們發現在施打tamoxifen 八周後,側腦室下區的神經幹細胞、神經母細胞、正在分裂的細胞與嗅球中新生的神經元皆有明顯的下降。因此之後我們選擇在施打完tamoxifen 後六周的母鼠與公鼠交配,並計算懷孕率。我們發現,這些缺少嗅球神經元新生的老鼠無法成功懷孕。我們的研究顯示嗅球神經元新生對於齧齒類生殖行為是必要的。

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricles can give rise to neuroblasts that migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB) and differentiate into interneurons. The OB consists of the main (MOB) and accessory olfactory bulb (AOB). MOB is involved in the perception of odorants. On the other hand, AOB responses to pheromonal cues. Pheromonal olfaction is critical for innate olfactory behaviors in rodents. Among them, an interesting phenomenon called the Bruce effect is that pheromones from the urine of males can re-initiate a female’s estrus cycle to cause pregnancy block. However, a female animal can form an “olfactory memory” specifically to the pheromones of its mate, so it will not reenter the estrus cycle after mating and has a miscarriage. Previously, we found that male pheromone-induced adult AOB neurogenesis was attenuated when females were exposed to pheromones from an unfamiliar male. This suggests that decrease of adult AOB neurogenesis contributes to the Bruce effect. To test this hypothesis, we genetically ablated adult neurogenesis by treating tamoxifen to Nestin-CreER; Rosa26-loxP-STOP-loxP-diphtheria toxin fragment A (R26-DTA) mice. In these mice, tamoxifen-induced Cre recombinase results in the expression of DTA in neural stem cells and causes their death. We found that neural stem cells, neuroblasts, proliferating cells in the SVZ and new neurons in the OB were decreased in double transgenic mice eight weeks after tamoxifen treatments. The neuronal density in the OB was decreased eight weeks after tamoxifen treatments, suggesting that adult OB neurogenesis is blocked in these mice. We performed mating experiment six weeks after tamoxifen treatments and found that tamoxifen-treated double transgenic female mice had lower pregnancy rate. This result suggests that adult OB neurogenesis is required for reproduction.

    摘要 3 Abstract 5 Introduction Adult neurigenesis 7 The olfactory system 8 Pheromones and social behaviors 9 Bruce effect 10 Cre/Loxp system (genetic ablation) 10 Hypothesis 12 Materials and Methods Experimental animals 13 Tamoxifen treatments 13 BrdU administrations 14 Perfusion and tissue preparation 14 Immunohistochemistry 14 Confocal and statistics analysis 16 Pregnacy test 16 Results 18 Discussion 22 Figures 27 References 39

    Altman, J. (1962). Are new neurons formed in the brains of adult mammals? Science 135, 1127-1128.
    Alvarez-Buylla, A., and Garcı́a-Verdugo, J.M. (2002). Neurogenesis in Adult Subventricular Zone. The Journal of Neuroscience 22, 629-634.
    Arisi, G.M., Foresti, M.L., Mukherjee, S., and Shapiro, L.A. (2012). The role of olfactory stimulus in adult mammalian neurogenesis. Behavioural brain research 227, 356-362.
    Belnoue, L., Grosjean, N., Abrous, D.N., and Koehl, M. (2011). A critical time window for the recruitment of bulbar newborn neurons by olfactory discrimination learning. The Journal of neuroscience : the official journal of the Society for Neuroscience 31, 1010-1016.
    Brennan, P.A., and Zufall, F. (2006). Pheromonal communication in vertebrates. Nature 444, 308-315.
    Breton-Provencher, V., Lemasson, M., Peralta, M.R., 3rd, and Saghatelyan, A. (2009). Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execution of selected olfactory behaviors. The Journal of neuroscience : the official journal of the Society for Neuroscience 29, 15245-15257.
    Breton-Provencher, V., and Saghatelyan, A. (2012). Newborn neurons in the adult olfactory bulb: unique properties for specific odor behavior. Behavioural brain research 227, 480-489.
    Bruce, H.M. (1963). Olfactory Block to Pregnancy among Grouped Mice. J Reprod Fertil 6, 451-460.
    Burns, K.A., Ayoub, A.E., Breunig, J.J., Adhami, F., Weng, W.L., Colbert, M.C., Rakic, P., and Kuan, C.Y. (2007). Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia hypoxia. Cereb Cortex 17, 2585-2592.
    Crusio, W.E. (2008). What’s Wrong with My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. Genes, Brain and Behavior 7, 831-831.
    Doetsch, F., and Hen, R. (2005). Young and excitable: the function of new neurons in the adult mammalian brain. Current opinion in neurobiology 15, 121-128.
    Dulac, C., and Torello, A.T. (2003). Molecular detection of pheromone signals in mammals: from genes to behaviour. Nature reviews Neuroscience 4, 551-562.
    Feierstein, C.E. (2012). Linking adult olfactory neurogenesis to social behavior. Frontiers in neuroscience 6, 173.
    Fendt, M., and Endres, T. (2008). 2,3,5-Trimethyl-3-thiazoline (TMT), a component of fox odor - just repugnant or really fear-inducing? Neurosci Biobehav Rev 32, 1259-1266.
    Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., Mori, K., Ikeda, T., Itohara, S., and Kageyama, R. (2008). Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nature neuroscience 11, 1153-1161.
    Inokuchi, K. (2011). Adult neurogenesis and modulation of neural circuit function. Curr Opin Neurobiol 21, 360-364.
    Knaden, M., and Hansson, B.S. (2014). Mapping odor valence in the brain of flies and mice. Current opinion in neurobiology 24, 34-38.
    Larsen, C.M., and Grattan, D.R. (2010). Prolactin-induced mitogenesis in the subventricular zone of the maternal brain during early pregnancy is essential for normal postpartum behavioral responses in the mother. Endocrinology 151, 3805-3814.
    Lau, B.W., Lee, J.C., Li, Y., Fung, S.M., Sang, Y.H., Shen, J., Chang, R.C., and So, K.F. (2012). Polysaccharides from wolfberry prevents corticosterone-induced inhibition of sexual behavior and increases neurogenesis. PLoS One 7, 16.
    Lazarini, F., and Lledo, P.M. (2011). Is adult neurogenesis essential for olfaction? Trends in neurosciences 34, 20-30.
    Lazarini, F., Mouthon, M.A., Gheusi, G., de Chaumont, F., Olivo-Marin, J.C., Lamarque, S., Abrous, D.N., Boussin, F.D., and Lledo, P.M. (2009). Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice. PLoS One 4, 0007017.
    Leuner, B., Glasper, E.R., and Gould, E. (2010). Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones. PLoS One 5, e11597.
    Leuner, B., Gould, E., and Shors, T.J. (2006). Is there a link between adult neurogenesis and learning? Hippocampus 16, 216-224.
    Liu, Y.H., Lai, W.S., Tsay, H.J., Wang, T.W., and Yu, J.Y. (2013). Effects of maternal immune activation on adult neurogenesis in the subventricular zone-olfactory bulb pathway and olfactory discrimination. Schizophr Res 151, 1-11.
    Lledo, P.M., Alonso, M., and Grubb, M.S. (2006). Adult neurogenesis and functional plasticity in neuronal circuits. Nature reviews Neuroscience 7, 179-193.
    Lledo, P.M., and Lazarini, F. (2007). Neuronal replacement in microcircuits of the adult olfactory system. Comptes rendus biologies 330, 510-520.
    Mak, G.K., Enwere, E.K., Gregg, C., Pakarainen, T., Poutanen, M., Huhtaniemi, I., and Weiss, S. (2007). Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nature neuroscience 10, 1003-1011.
    Mak, G.K., and Weiss, S. (2010). Paternal recognition of adult offspring mediated by newly generated CNS neurons. Nat Neurosci 13, 753-758.
    Ming, G.L., and Song, H. (2011). Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70, 687-702.
    Moreno, M.M., Linster, C., Escanilla, O., Sacquet, J., Didier, A., and Mandairon, N. (2009). Olfactory perceptual learning requires adult neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 106, 17980-17985.
    Nunez-Parra, A., Pugh, V., and Araneda, R.C. (2011). Regulation of adult neurogenesis by behavior and age in the accessory olfactory bulb. Mol Cell Neurosci 47, 274-285.
    Oboti, L., Savalli, G., Giachino, C., De Marchis, S., Panzica, G.C., Fasolo, A., and Peretto, P. (2009). Integration and sensory experience-dependent survival of newly-generated neurons in the accessory olfactory bulb of female mice. Eur J Neurosci 29, 679-692.
    Oboti, L., Schellino, R., Giachino, C., Chamero, P., Pyrski, M., Leinders-Zufall, T., Zufall, F., Fasolo, A., and Peretto, P. (2011). Newborn interneurons in the accessory olfactory bulb promote mate recognition in female mice. Frontiers in neuroscience 5, 113.
    Paton, J.A., and Nottebohm, F.N. (1984). Neurons generated in the adult brain are recruited into functional circuits. Science 225, 1046-1048.
    Peele, P., Salazar, I., Mimmack, M., Keverne, E.B., and Brennan, P.A. (2003). Low molecular weight constituents of male mouse urine mediate the pregnancy block effect and convey information about the identity of the mating male. Eur J Neurosci 18, 622-628.
    Portillo, W., Unda, N., Camacho, F.J., Sanchez, M., Corona, R., Arzate, D.M., Diaz, N.F., and Paredes, R.G. (2012). Sexual activity increases the number of newborn cells in the accessory olfactory bulb of male rats. Frontiers in neuroanatomy 6, 25.
    Sahay, A., and Hen, R. (2007). Adult hippocampal neurogenesis in depression. Nature neuroscience 10, 1110-1115.
    Sakamoto, M., Imayoshi, I., Ohtsuka, T., Yamaguchi, M., Mori, K., and Kageyama, R. (2011). Continuous neurogenesis in the adult forebrain is required for innate olfactory responses. Proceedings of the National Academy of Sciences of the United States of America 108, 8479-8484.
    Sakano, H. (2010). Neural map formation in the mouse olfactory system. Neuron 67, 530-542.
    Sharrow, S.D., Vaughn, J.L., Zidek, L., Novotny, M.V., and Stone, M.J. (2002). Pheromone binding by polymorphic mouse major urinary proteins. Protein Sci 11, 2247-2256.
    Singh, P.B. (2001). Chemosensation and genetic individuality. Reproduction 121, 529-539.
    Sultan, S., Mandairon, N., Kermen, F., Garcia, S., Sacquet, J., and Didier, A. (2010). Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory. Faseb J 24, 2355-2363.
    Thompson, R.N., McMillon, R., Napier, A., and Wekesa, K.S. (2007). Pregnancy block by MHC class I peptides is mediated via the production of inositol 1,4,5-trisphosphate in the mouse vomeronasal organ. The Journal of experimental biology 210, 1406-1412.
    Wu, J.H., Han, Y.T., Yu, J.Y., and Wang, T.W. (2013). Pheromones from males of different familiarity exert divergent effects on adult neurogenesis in the female accessory olfactory bulb. Developmental neurobiology 73, 632-645.
    Yamashita, Y.M., Yuan, H., Cheng, J., and Hunt, A.J. (2010). Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. Cold Spring Harbor perspectives in biology 2, a001313.
    Yamazaki, K., Beauchamp, G.K., Curran, M., Bard, J., and Boyse, E.A. (2000). Parent-progeny recognition as a function of MHC odortype identity. Proceedings of the National Academy of Sciences of the United States of America 97, 10500-10502.
    Zhao, C., Deng, W., and Gage, F.H. (2008). Mechanisms and functional implications of adult neurogenesis. Cell 132, 645-660.

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