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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 黃佩欣(Pei-Hsin Huang) | |
dc.contributor.author | Tsung-Ying Yang | en |
dc.contributor.author | 楊宗穎 | zh_TW |
dc.date.accessioned | 2021-06-08T02:48:44Z | - |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-18 | |
dc.identifier.citation | 1. Susan Elmore. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol. 2007; 35(4): 495–516.
2. Green DR, Llambi F. Cell Death Signaling. Cold Spring Harb Perspect Biol. 2015 Dec 1;7(12). 3. Nu ZHANG, Heather HARTIG. The role of apoptosis in the development and function of T lymphocytes. Cell Research (2005) 15, 749–769. 4. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Eng J Med. 2009 Oct 15;361(16):1570-83. 5. Strasser A, Cory S, Adams JM. Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J 2011; 30: 3667–3683. 6. Kischkel FC, Hellbardt S. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 1995 Nov 15;14(22):5579-88. 7. Autret A, Martin SJ. Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis. Mol Cell. 2009 Nov 13;36(3):355-63. 8. Hua C, Raffeld M, Ko HS. Mechanism of bcl-2 activation in human follicular lymphoma. Oncogene. 1990 Feb;5(2):233-5. 9. Hockenbery DM. bcl-2 in cancer, development and apoptosis. J Cell Sci Suppl. 1994;18:51-5. 10. Lutz RJ. Role of the BH3 (Bcl-2 homology 3) domain in the regulation of apoptosis and Bcl-2-related proteins. Biochem Soc Trans. 2000 Feb;28(2):51-6. 11. M Giam, T Okamoto, J D Mintern. Bcl-2 family member Bcl-G is not a proapoptotic protein. Cell Death Dis. 2012 Oct; 3(10): e404. 12. J J Hunter, B L Bond, and T G Parslow. Functional dissection of the human Bc12 protein: sequence requirements for inhibition of apoptosis. Mol Cell Biol. 1996 Mar; 16(3): 877–883. 13. Cory S, Huang DC, Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003 Nov 24;22(53):8590-607. 14. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9: 47–59. 15. Giam M, Huang DC, Bouillet P. BH3-only proteins and their roles in programmed cell death. Oncogene 2008; 27: S128–S136. 16. Veis DJ, Sorenson CM, Shutter JR. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 1993 Oct 22;75(2):229-40. 17. Rinkenberger JL, Horning S, Klocke B. Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes Dev. 2000 Jan 1;14(1):23-7. 18. Motoyama N, Wang F, Roth KA. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science. 1995 Mar 10;267(5203):1506-10. 19. Hardwick JM, Soane L. Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2). 20. Eckenrode EF. Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling. J Biol Chem. 2010 Apr 30;285(18):13678-84. 21. Karch J, Kwong JQ, Burr AR. Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice. Elife. 2013 Aug 27;2:e00772. 22. Danial NN, Gramm CF, Scorrano L. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature. 2003 Aug 21;424(6951):952-6. 23. Liu Y, Aiello A, Zinkel SS. Bid protects the mouse hematopoietic system following hydroxyurea-induced replicative stress. Cell Death Differ. 2012 Oct;19(10):1602-12. 24. Gross A, Katz SG. Non-apoptotic functions of BCL-2 family proteins. Cell Death Differ. 2017 Aug;24(8):1348-1358. 25. Wei-Wen Liu, Hwai-Jong Cheng, Pei-Hsin Huang. Blm-s, a BH3-Only Protein Enriched in Postmitotic Immature Neurons, Is Transcriptionally Upregulated by p53 during DNA Damage. Cell Reports 9, 166–179 October 9, 2014. 26. Charles V Vorhees and Michael T Williams. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006; 1(2): 848–858. 27. Daniela Bermpohl et al. Traumatic brain injury in mice deficient in Bid: effects on histopathology and functional outcome. Journal of Cerebral Blood Flow & Metabolism (2006) 26, 625–633. 28. Han-Ying Wang et al. RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function. Scientific Reports, DOI: 10.1038 (2015). 29. Deacon, R.M. Measuring Motor Coordination in Mice. J. Vis. Exp. (75), e2609, doi:10.3791/2609 (2013). 30. Michelle C Potter et al. Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease. PLoS Curr. (2010) December 7; 2: RRN1201. 31. Hiromi Shiotsuki et al. A rotarod test for evaluation of motor skill learning. Journal of Neuroscience Methods. 189 (2010) 180–185. 32. Yi-Sian Lin et al. Neuronal Splicing Regulator RBFOX3 (NeuN) Regulates Adult Hippocampal Neurogenesis and Synaptogenesis. PLOS ONE. (2016) DOI:10.1371. 33. Laura Inocencio Leite et al. Antinociceptive action of Vanillosmopsis arborea in male mice. AJP, Vol. 7, No. 1, Jan-Feb 2017. 34. M.D. Sanna et al. PKC-mediated HuD–GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy. Pharmacological Research 81 (2014) 44–53. 35. Zsuzsanna Helyes et al. Hemokinin-1 mediates anxiolytic and anti-depressant-like actions in mice. Brain Behav Immun. 2017 Jan; 59:219-232. 36. Can, A., Dao, D.T., Arad, M., Terrillion, C.E., Piantadosi, S.C., Gould, T.D. The Mouse Forced Swim Test. J. Vis. Exp. (59), e3638, DOI : 10.3791/3638 (2012). 37. QianWang et al. The anxiolytic- and antidepressant-like effects of ATPM-ET, a novel κ agonist and μ partial agonist, in mice. Psychopharmacology (2016) 233:2411–2418. 38. Attila D. Kovács1 and David A. Pearce. Finding the most appropriate mouse model of juvenile CLN3 (Batten) disease for therapeutic studies: the importance of genetic background and gender. The Company of Biologists Ltd, Disease Models & Mechanisms (2015) 8, 351-361. 39. Can, A., Dao, D.T., Terrillion, C.E., Piantadosi, S.C., Bhat, S., Gould, T.D. The Tail Suspension Test. J. Vis. Exp. (59), e3769, doi:10.3791/3769 (2012). 40. Van Calker, D. and Biber, K. Sucrose Preference Test to Measure Anhedonic Behaviour in Mice. Bio-protocol. Vol 6, Iss 19, Oct 05, 2016. 41. Grillo L. Might the inability to feel pleasure (anhedonia) explain the symptoms of major depression and schizophrenia, including unmotivated anxiety, delusions and hallucinations? Med Hypotheses. 2012 Jan;78(1):98-101. 42. Li YC, Wang LL, Pei YY. Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone. Neuroscience. 2015 Dec 17;311:130-7. 43. Campos AC, Rocha NP, Nicoli JR. Absence of gut microbiota influences lipopolysaccharide-induced behavioral changes in mice. Behav Brain Res. 2016 Oct 1;312:186-94. 44. Munekazu Komada, Keizo Takao, and Tsuyoshi Miyakawa. Elevated Plus Maze for Mice. J Vis Exp. 2008; (22): 1088. 45. Guimarães ATB, de Oliveira Ferreira R, de Souza JM. Anxiety and memory deficits induced by tannery effluent in C57BL/6J female mice. Environ Sci Pollut Res Int. 2016 Dec;23(24):25323-25334. 46. Borbély É, Hajna Z, Nabi L. Hemokinin-1 mediates anxiolytic and anti-depressant-like actions in mice. Brain Behav Immun. 2017 Jan;59:219-232. 47. Wang Q, Long Y, Hang A. The anxiolytic- and antidepressant-like effects of ATPM-ET, a novel κ agonist and μ partial agonist, in mice. Psychopharmacology (Berl). 2016 Jun;233(12):2411-8. 48. Pyter LM, Pineros V, Galang JA. Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation. Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9069-74. 49. V Mosienko, B Bert, D Beis. Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin. Translational Psychiatry (2012) 2, e122. 50. Ibrahim S, Hu W, Wang X. Traumatic Brain Injury Causes Aberrant Migration of Adult-Born Neurons in the Hippocampus. Sci Rep. 2016 Feb 22;6:21793. 51. Rendeiro C, Sheriff A, Bhattacharya TK. Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer. Behav Brain Res. 2016 Dec 15;315:10-22. 52. Hashimoto M, Hibi M. Development and evolution of cerebellar neural circuits. Dev Growth Differ. 2012 Apr;54(3):373-89. 53. Jin J, Maren S. Prefrontal-Hippocampal Interactions in Memory and Emotion. Front Syst Neurosci. 2015 Dec 15;9:170. 54. Thomason ME, Hamilton JP, Gotlib IH. Stress-induced activation of the HPA axis predicts connectivity between subgenual cingulate and salience network during rest in adolescents. J Child Psychol Psychiatry. 2011 Oct;52(10):1026-34. 55. Elizabeth N. Holly and Klaus A. Miczek. Ventral tegmental area dopamine revisited: effects of acute and repeated stress. Psychopharmacology (Berl). 2016 Jan; 233(2): 163–186. 56. Kheirbek, M. A. et al. Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus. Neuron. 2013, 77, 955–968. 57. Deacon, R. M. & Rawlins, J. N. Hippocampal lesions, species-typical behaviours and anxiety in mice. Behav Brain Res. 2005, 156, 241–249. 58. Mazen A Kheirbek and René Hen. Dorsal vs Ventral Hippocampal Neurogenesis: Implications for Cognition and Mood. Neuropsychopharmacology (2011) 36, 373–374. 59. Philip Tovote, Jonathan Paul Fadok and Andreas Lüthi. Neuronal circuits for fear and anxiety. Nat Rev Neurosci. 2015 Jun;16(6):317-31. 60. Charles V Vorhees and Michael T Williams. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006; 1(2): 848–858. 61. Brandon C. McKinney, Clement Y. Chow. Exaggerated emotional behavior in mice heterozygous for the sodium channel Scn8a. Genes Brain Behav. 2008 Aug; 7(6): 629–638. 62. Eisch AJ, Petrik D. Depression and hippocampal neurogenesis: a road to remission? Science. 2012 Oct 5;338(6103):72-5. 63. Duman RS, Aghajanian GK. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012 Oct 5;338(6103):68-72. 64. Sarosiek KA1, Letai A. Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise. FEBS J. 2016 Oct;283(19):3523-3533. 65. Coultas L, Bouillet P, Loveland KL. Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis. EMBO J. 2005 Nov 16;24(22):3963-73. 66. Lomonosova E, Chinnadurai G. BH3-only proteins in apoptosis and beyond: an overview. Oncogene. 2008 Dec;27. 67. Hetz C1, Glimcher L. The daily job of night killers: alternative roles of the BCL-2 family in organelle physiology. Trends Cell Biol. 2008 Jan;18(1):38-44. 68. Chattopadhyay A, Chiang CW, Yang E. BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest. Oncogene. 2001 Jul 27;20(33):4507-18. 69. Mok CL. Bad can act as a key regulator of T cell apoptosis and T cell development. J Exp Med. 1999 Feb 1;189(3):575-86. 70. Danial NN. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature. 2003 Aug 21;424(6951):952-6. 71. Zinkel SS, Hurov KE, Ong C, Abtahi FM, Gross A, Korsmeyer SJ. A role for proapoptotic BID in the DNA-damage response. Cell. 2005 Aug 26;122(4):579-91. 72. Esposti MD, Erler JT, Hickman JA, Dive C. Bid, a widely expressed proapoptotic protein of the Bcl-2 family, displays lipid transfer activity. Mol Cell Biol. 2001 Nov;21(21):7268-76. 73. Nakajima K. Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion. EMBO J. 2004 Aug 18;23(16):3216-26. Epub 2004 Jul 22. 74. Zeng X, Overmeyer JH, Maltese WA. Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J Cell Sci. 2006 Jan 15;119(Pt 2):259-70. Epub 2006 Jan 3. 75. Maiuri MC. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 2007 May 16;26(10):2527-39. Epub 2007 Apr 19. 76. Elgendy M, Sheridan C, Brumatti G, Martin SJ. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival. Mol Cell. 2011 Apr 8;42(1):23-35. 77. Herold MJ. Evidence against upstream regulation of the unfolded protein response (UPR) by pro-apoptotic BIM and PUMA. Cell Death Dis. 2014 Jul 31;5:e1354. 78. Schmidt EF, Warner-Schmidt JL, Otopalik BG. Identification of the cortical neurons that mediate antidepressant responses. Cell. 2012 May 25;149(5):1152-63. 79. Petrik D, Lagace DC, Eisch AJ. The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Neuropharmacology. 2012 Jan;62(1):21-34. 80. Petrik D, Lagace DC, Eisch AJ. The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Neuropharmacology. 2012 Jan;62(1):21-34. 81. Sahay A, Hen R. Hippocampal neurogenesis and depression. Novartis Found Symp. 2008;289:152-60. 82. Squire LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992 Apr;99(2):195-231. 83. Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 2010 May;11(5):339-50. 84. Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008 Oct 16;455(7215):894-902. 85. Duman RS, Voleti B. Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci. 2012 Jan;35(1):47-56. 86. Xu J, Zhang QG, Li C, Zhang GY. Subtoxic N-methyl-D-aspartate delayed neuronal death in ischemic brain injury through TrkB receptor- and calmodulin-mediated PI-3K/Akt pathway activation. Hippocampus. 2007;17(7):525-37. 87. Huang TY, Lin CH. Role of amygdala MAPK activation on immobility behavior of forced swim rats. Behav Brain Res. 2006 Oct 2;173(1):104-11. 88. Marsden WN. Synaptic plasticity in depression: molecular, cellular and functional correlates. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jun 3;43:168-84. doi: 10.1016/j.pnpbp.2012.12.012. Epub 2012 Dec 23. 89. Banasr M, Dwyer JM, Duman RS. Cell atrophy and loss in depression: reversal by antidepressant treatment. Curr Opin Cell Biol. 2011 Dec;23(6):730-7. 90. Li X, Jope RS. Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology. 2010 Oct;35(11):2143-54. 91. Beaulieu JM, Gainetdinov RR, Caron MG. Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol. 2009;49:327-47. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20438 | - |
dc.description.abstract | BLM-s是BCL-2家族成員中的一員,大量存在於發育中大腦皮質的postmitotic neurons,具有可以誘導細胞進行凋亡(apoptosis)的功能。我們利用同源重組的方式已經製備出Blm-s的基因剃除小鼠(knockout mice)。基因剔除鼠在外觀以及健康上皆屬正常,且具有正常的生育能力,其子代皆嚴格遵守孟德爾遺傳定律(Mendelian heredity rule)。在各個主要器官中,不論是外觀或是組織型態,皆不會因為Blm-s基因的剃除而導致任何顯著上的異常。此外,我們發現BLM-s特別在杏仁核(amygdala)、海馬迴(hippocampus)以及內側前額葉皮層(medial prefrontal cortex)中的某些神經細胞中進行表現。由於這些腦區被認為參與記憶以及情緒的調控,因此我們首先針對這些基因剃除小鼠進行學習以及記憶行為的探討。在Morris水迷宫(Morris water maze)的試驗中,Blm-s基因剃除小鼠在空間學習以及記憶行為的表現上皆屬正常,然而卻在適應期時呈現不游動的異常表現。這樣的結果顯示了Blm-s基因的剃除,有可能導致小鼠在情緒的調控上表現異常。因此,我們更進一步進行其他與情緒調控相關的動物行為試驗,像是強迫游泳試驗(forced swimming test)、懸尾試驗(tail suspension test)、舉臂式十字迷宮試驗(elevated plus-maze test)以及曠野實驗(open field test)。其結果皆表明Blm-s基因剃除小鼠可能表現出憂鬱或焦慮的異常行為特徵。更進一步的研究顯示,這樣的一個行為表徵有可能是因為海馬迴神經的生成異常以及齒狀回(dentate gyrus)樹突棘(dendritic spine)的複雜度減少所導致。綜合上述實驗,我們的研究結果發現BLM-s具有其他非細胞凋亡(non-apoptotic)的新功能,尤其是在調控情緒以及壓力有關的神經迴路 (neurocircuitry),其細胞/分子的訊息傳遞以及生成中扮演著相當重要的一個角色。 | zh_TW |
dc.description.abstract | Blm-s (Bcl-2-like molecule, short form) is one of the Bcl-2 family member. It abounds in postmitotic neurons of the developing cerebral cortex and functions as a BH3-only apoptosis sensitizer/derepressor to mediate apoptosis of the immature migratory postmitotic neurons. We have generated conventional Blm-s knockout mice through genomic homologous recombination strategy. These Blm-s-KO mice have normal outlook, appear healthy and live to the expected life. They also show normal fertility and the genotype of their descendants strictly follow the autosomal Mendelian heredity rule. There is no obvious abnormality in their internal organ grossly. Microscopically, we found BLM-s is expressed in layer V of the medial prefrontal cortex (mPFC), hippocampus, and in some subsets of neurons in amygdala, which disappears in Blm-s-KO mice. Since these brain regions are involved in memory and emotional regulation, we investigate the memory and learning behaviors of Blm-s-KO mice. Blm-s-KO mice show normal spatial learning and memory performance by Morris water maze (MWM) test, but they exhibit poorer mobility in adaption period. These results suggest that the Blm-s-KO have emotional changes. Thus, we performed forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM) and open field test (OFT) to demonstrate that Blm-s-KO mice indeed exhibit depression and/or anxiety behaviors. Moreover, further study demonstrates that decreased hippocampal adult neurogenesis and decreased dendritic spine complexity possibly contribute to these behavioral phenotypes observed in Blm-s-KO mice. Collectively, our results uncover a novel non-apoptotic function of BLM-s and reveal that BLM-s might play an important role in the regulation of developmental or cellular/molecular processes of neurocircuitry involved in emotional or stress control. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:48:44Z (GMT). No. of bitstreams: 1 ntu-106-R04444003-1.pdf: 4159863 bytes, checksum: 71ac8a9a52d6f70a54fee2363d71d54b (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii ABSTRACT iii CONTENTS v Introduction 1 1. Brief introduction to apoptosis 1 2. The BCL-2 family 1 3. Multiple biological functions of the BCL-2 family proteins 2 4. BLM-s, a BH3-only protein of the BCL-2 family, is expressed in developing mammalian embryonic brains 3 Materials and Methods 5 1. Animals 5 2. Genotyping 5 3. RT-PCR analysis 6 4. Western blotting 6 5. Tissue preparation 7 6. Histology 7 7. γ-irradiation (γ-IR) administration 7 8. TUNEL assay 8 9. Immunohistochemistry (IHC) 8 10. Morris water maze (MWM) test 9 11. Rotarod performance test 9 12. Hot/cold plate test 10 13. Forced swimming test (FST) 10 14. Tail suspension test (TST) 11 15. Sucrose preference test (SPT) 11 16. Elevated plus maze (EPM) test 12 17. Open field test (OFT) 12 18. Marble burying test (MBT) 13 19. Novelty suppressed feeding (NSF) test 13 20. BrdU and Ki67 labeling 13 21. Golgi-Cox staining 14 22. Statistical analysis 15 Results 16 1. Validation of the Blm-s null mice 16 2. No global abnormality was observed in Blm-s knockout mice 16 3. Loss of Blm-s did not cause significant defects in brain morphology in either postnatal or embryonic mice 17 4. Blm-s knockout partially prevents γ-irradiation triggered-apoptosis of postmitotic migratory neurons in the developing embryonic cortex 18 5. BLM-s was detected in a subset of neurons in amygdala, cortex, hippocampus, and cerebellum 18 6. Blm-s-KO mice show poor mobility but normal acquisition in MWM task 19 7. No abnormal thermal sensation or compromised locomotion in Blm-s-KO mice 20 8. Blm-s-KO mice exhibited generalized anxiety and depressive-like behaviors 21 9. Decreased adult hippocampal neurogenesis and simplified dendritic branching pattern of hippocampal granular cells in Blm-s-KO mice 22 10. Dysregulated GSK3β and MAPK signaling in adult hippocampus of Blm-s-KO mice 24 Discussion 26 1. Lack of changes in cell density of cerebral cortex in Blm-s-deficient mice: a possible role of functional redundancy of members of the BCL-2 superfamily 26 2. Blm-s-KO mice exhibit emotional change, but show normal spatial learning and memory performance in MWM task 27 3. Dysregulated adult hippocampal neurogenesis could underlie depression /anxiety observed in Blm-s-KO mice 28 4. Blm-s-KO mice reveal dysregulated GSK3β and MAPK signaling in adult hippocampus 29 5. Non-apoptotic functions of the BCL-2 family members: an implication of novel BLM-s function other than cell death in adult mouse brain 30 Tables 32 Table 1. Male and Female ratio 32 Table 2. Offspring ratio 32 Figures and Figure legends 33 Figure 1. Generation of Blm-s-KO mice. 33 Figure 2. Phenotypic characterization of Blm-s-KO mice. 35 Figure 3. Assessment of the brain morphology from postnatal or embryonic Blm-s-KO mice 37 Figure 4. Reduced apoptosis of E16.5 embryonic cortex of Blm-s-KO mice treated with γ-IR 39 Figure 5. Expression of BLM-s in distinct brain regions 41 Figure 6. Blm-s-KO mice displayed poorer mobility in adaptation period during MWM test 43 Figure 7. Blm-s-KO mice exhibited normal locomotor activity and thermal sensation 45 Figure 8. Assessment of depression-like behavior in Blm-s-KO mice. 47 Figure 9. Evaluation of anxiety-like behavior in Blm-s-KO mice. 49 Figure 10. Loss of BLM-s impaired hippocampal adult neurogenesis 52 Figure 11. Granule cells of Blm-s-KO mice exhibited decreased spine density and dendritic complexity 55 Figure 12. Dysregulated expression of molecules involved in GSK3β and MAPK signaling in adult hippocampus of Blm-s-KO mice 57 REFERENCE 59 | |
dc.language.iso | en | |
dc.title | BLM-s,BCL-2家族的一員,之新穎功能發現:參與憂鬱以及焦慮情緒的調控 | zh_TW |
dc.title | BLM-s, a BH3-Only Protein, Functions in Mood Control | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃憲松(Hsien-Sung Huang),姚皓傑(Hau-Jie Yau) | |
dc.subject.keyword | Blm-s基因剃除小鼠,憂鬱,焦慮,老鼠動物行為試驗,海馬迴神經元新生, | zh_TW |
dc.subject.keyword | Blm-s-KO mice,depression,anxiety,mouse behavioral test,hippocampal adult neurogenesis, | en |
dc.relation.page | 67 | |
dc.identifier.doi | 10.6342/NTU201703504 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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