博碩士論文 112821013 詳細資訊




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姓名 廖昱雅(Yu-Ya Liao)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 探討壓力對觀察恐懼學習的影響: 雄性小鼠杏仁核腦區分子機制探討
(Investigate the Impact of Stress and Observational Fear Learning: Mechanisms in the Amygdala of male mice)
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檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2029-6-30以後開放)
摘要(中) 壓力是誘導精神障礙的潛在因子,研究證實壓力會影響大腦神經機制與行為表現。觀察恐懼學習是指透過觀察他人的情緒表達而學習恐懼的過程,可以促進個體適應厭惡性刺激,在精神障礙患者中觀察恐懼學習缺失為常見的症狀之一。本實驗室先前的研究指出雙重壓力會降低雄性小鼠觀察恐懼學習並降低杏仁核神經活性,然而壓力與觀察恐懼學習之間的分子機制並不清楚,因此本論文將利用雄性壓力小鼠模型進一步探討壓力與觀察恐懼學習之間的分子機制。首先將各組壓力與對照組小鼠杏仁核組織進行RNA定序,定序結果指出雙重壓力與觀察恐懼學習影響下降低大部分差異表現基因的表達,分析後有81個基因僅顯著差異表達於雙重壓力雄性小鼠,81個基因經過生物過程基因體分析後指出雙重壓力與觀察恐懼學習主要影響髓鞘以及膠細胞相關途徑,例如Cntn2和Sgpp2。接著我們利用聚合酶鏈鎖反應檢測各組壓力與對照組小鼠杏仁核髓鞘和膠細胞相關基因表達量,發現壓力與觀察恐懼學習確實降低Cntn2 以及Mbp在杏仁核的表達。為了驗證雙重壓力與觀察恐懼學習是否共同影響杏仁核中髓鞘和膠細胞相關基因表現,我們同樣利用聚合酶鏈鎖反應檢測 Naïve-Ctrl、Naïve-DS、OFL-Ctrl以及OFL-DS小鼠杏仁核Cntn2和Sgpp2表達,本論文發現Sgpp2的表達會受到雙重壓力和觀察恐懼學習的影響而下降。由於文獻表明血清素、催產素和多巴胺系統與精神
障礙有高度相關,同時我們也在RNA定序中發現這些基因可能參與調控雙重壓力與觀察恐懼學習,因此我們利用相同實驗方式對相關基因進行探討。本論文表明雙重壓力與觀察恐懼學習會降低杏仁核CD38以及增加Oxt與SLC6A4表達,另外也證明這些基因表達變化確實是受到雙重壓力與觀察恐懼學習共同的影響。綜合上述結果表明杏仁核髓鞘形成、血清素和催產素系統參與調控雄性小鼠雙重壓力與觀察恐懼學習的行為,也為精神障礙中觀察恐懼學習缺失的機制提供進一步見解。
摘要(英) Stress is known to increase the risk of mental illness. Previous studies have shown that stress affects both neuronal mechanisms in the brain and behavior. Observational fear, the process of learning fear through others, helps individuals adapt to negative stimuli, and its impairment is a common symptom in patients with mental illness. In our preliminary data, we found that male DS-Ob mice exhibited reduced freezing time during observational fear learning
test and decreased neural activity in the amygdala. However, the underlying mechanisms linking stress and observational fear learning remain unclear. In this study, we used a male
stressed-mice model to investigate this mechanism. We first performed RNA sequencing on the amygdala of each stressed mouse and found that 81 differentially expression genes were
downregulated in male DS-Ob mice. Gene Ontology (GO) analysis indicated that these genes are involved in myelin sheath formation and glial cell function, including genes such as Cntn2 and Sgpp2. Furthermore, we examined the mRNA expression of myelin-related genes in the amygdala of stressed male mice using qPCR, which revealed decreased expression of these genes in male DS-Ob mice. Given that serotonin, oxytocin and dopamine systems are frequently
implicated in mental illness, we also identified these systems in our RNA sequencing data as being related to doubled-stress and observational fear learning.Specifically, we found that the expression of CD38 decreased, while Oxt and SLC6A4 increased in male DS-Ob mice, as confirmed by qPCR. To determine whether these genes are involved in both doubled-stress and observational fear learning, we compared mRNA expression levels between Naïve and OFL groups, with or without doubled-stress. Our results showed that Sgpp2 and CD38 decreased, while Oxt and SLC6A4 increased after doubled-stress and observational fear learning in the amygdala of male mice. In summary, this thesis demonstrates that myelination, serotonin, and oxytocin systems in the amygdala play a role in regulating doubled-stress and observational fear learning in male mice. These findings offer new insights into the mechanisms underlying observational fear learning impairment in stress-induced mental illness disorders.
關鍵字(中) ★ 雙重壓力
★ 觀察恐懼學習
★ 髓鞘形成
★ 血清素系統
★ 催產素系統
關鍵字(英) ★ doubled-stress
★ observational fear learning
★ myelination
★ serotonin system
★ oxytocin system
論文目次 目錄
中文摘要 I
英文摘要Abstract II
致謝 IV
圖目錄 VIII
表目錄 IX
中英文對照表 X
一、緒論 1
1-1壓力 1
1-2早期壓力 3
1-3慢性不可預測壓力 5
1-4壓力與血清素系統關聯 7
1-5壓力與催產素系統關聯 10
1-6壓力與多巴胺系統關聯 12
1-7觀察恐懼學習 14
1-8研究動機與目的 16
二、研究方法 17
2-1實驗動物 17
2-2建立小鼠壓力模型 17
2-2-1早期壓力小鼠模型 17
2-2-2慢性不可預測壓力小鼠模型 18
2-2-3雙重壓力小鼠模型 20
2-2-4對照組小鼠模型 20
2-3觀察恐懼學習實驗 21
2-4實驗小鼠犧牲與收組織 22
2-5 RNA萃取 23
2-6 RNA定序 23
2-7即時聚合酶鏈鎖反應 24
2-8統計分析 24
三、研究結果 25
3-1壓力與觀察恐懼學習影響雄性小鼠大腦神經活性 25
3-2壓力與觀察恐懼學習改變雄性小鼠杏仁核基因表達 25
3-3雄性小鼠杏仁核壓力與觀察恐懼學習的基因體分析 26
3-4探討壓力與觀察恐懼學習對杏仁核髓鞘相關基因表達 27
3-5探討雙重壓力與觀察恐懼學習對杏仁核髓鞘相關基因表達 27
3-6探討雙重壓力與觀察恐懼學習對杏仁核催產素相關基因表達 28
3-7探討雙重壓力與觀察恐懼學習對杏仁核血清素相關基因表達 28
3-8探討雙重壓力與觀察恐懼學習對杏仁核多巴胺相關基因表達 29
四、討論 30
五、結論 33
參考文獻 45
附錄 64
附件1、ELS雄性小鼠差異表現基因列表 64
附件2、CUS雄性小鼠差異表現基因列表 65
附件3、DS雄性小鼠差異表現基因列表 66
附件4、ELS與CUS雄性小鼠共同差異表現基因列表 67
附件5、ELS與DS雄性小鼠共同差異表現基因列表 68
附件6、CUS與DS雄性小鼠共同差異表現基因列表 69
附件7、ELS、CUS與DS雄性小鼠共同差異表現基因列表 70
附件8、ELS雄性小鼠特異性差異表現基因列表 71
附件9、CUS雄性小鼠特異性差異表現基因列表 72
附件10、DS雄性小鼠特異性差異表現基因列表 73
附件11、即時聚合酶鏈鎖反應引子序列 74
附件12、Supplementary figure 76
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指導教授 黃佳瑜(Chia-Yu Huang) 審核日期 2024-8-15
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