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標題: | 產前感染及社交隔離影響成年小鼠齒狀迴正常功能與結構 Prenatal infection and social isolation affect function and structure of the Dentate Gyrus in adult mice |
作者: | Yi-Chun Chang 張亦鈞 |
指導教授: | 李立仁 |
關鍵字: | 精神分裂症,聚??酸,社交隔離,空間記憶,齒狀迴,樹突分支,樹突棘,微膠細胞,抑制性神經元,寡樹突細胞, schizophrenia,Poly I:C,social isolation,spatial memory,dentate gyrus,dendritic architecture,spine,microglia,GABAergic neuron,oligodendrocyte., |
出版年 : | 2013 |
學位: | 碩士 |
摘要: | 現今精神分裂症患者約占全世界人口的百分之一。心智功能受損,情緒以及行為上的偏差是這些患者的主要徵狀,此外,認知處理,包含理解以及判斷能力皆會受到損害。促成精神分裂症發生的原因有很多,主要可區分三大類:基因缺陷,產前環境干擾,以及產後環境干擾。在本實驗中,我們試圖結合後兩種致病因子,探究個別效應,以及是否產生交互作用,使得小鼠表現出與精神分裂症相關行為的情況加劇。實驗方法如下,於B6母鼠懷孕第九天施打生理食鹽水或Poly I:C (20 mg/kg,腹腔注射) 模擬產前病毒感染。待其子代產出,離乳後(約產後第三十天)再分成單獨飼養,以及群體飼養組直到成年(約產後六十天)。之後,進行一系列的表現型檢測。首先,我們檢測與情緒向度相關之行為,雖然四個組別在架高十字迷宮的表現略同,但是,在強迫游泳的實驗中,則發現產前感染以及長期的隔離環境產生協同效應,使得小鼠於水中不動的時間明顯減少。接著,我們使用水迷宮檢測小鼠與海馬迴相關的空間學習能力是否發生改變。相較於控制組,產前感染合併長期社交隔離之小鼠學習能力下降。此外,所有經過社交隔離的小鼠皆出現記憶缺損現象。在形態學方面的研究,我們檢驗了齒狀迴顆粒細胞的樹突分支結構。在所有的實驗組,皆出現樹突複雜度以及棘突下降之現象。此外,產前感染Poly I:C組別,於出生後第二天統計海馬迴微膠細胞的數量,結果明顯高於產前未施打Poly I:C之組別,而這樣的現象在產後第八十天則消失,顯示產前感染的確造成胎兒的免疫系統被暫時性的活化。最後,我們分別檢驗齒狀迴中抑制性神經元以及寡樹突細胞的數量,所有的組別皆無達顯著差異,顯示產前感染以及長期隔離兩因子皆不會影響抑制性神經元以及寡樹突細胞的數量。整體來說,我們發現產前感染以及長期隔離兩因子之個別效應以及協同效應,影響齒狀迴正常結構及功能。這些結果顯示,產前感染以及不良社交孤立之交互作用對於精神疾病的相關性。 Schizophrenia affects approximately 1% of the population worldwide. Impaired mental functions, emotions and behaviors are characteristics of this disease; besides, cognitive processes including perception and judgment are also devastated in patients with schizophrenia. Multiple factors, including genetic defects, prenatal and postnatal environmental insults, are thought to be involved in the pathogenic process of the illness. In this study, we aimed to explore the singular and synergistic effects of factors of different origins that may interactively affect the behavioral performances related to schizophrenia in mice. We administered a viral mimic, polyriboinosinic- polyribocytidilic acid (Poly I:C, 20 mg/Kg, ip), to pregnant B6 mice at gestation day 9 to simulate prenatal immune challenge. After P30, male offspring were kept in group (group-rearing) or individually (isolation-rearing). After P60, phenotypes were characterized in various aspects. We first examined the emotion-related behaviors. Though there was no difference among four groups in elevated plus maze test, prenatal infection and long-term isolation produced synergistic effects on reducing immobility in the forced swimming test. We next evaluated the hippocampus-related cognitive functions using Morris water maze. Compared to the control group, impaired spatial memory was evident in mice treated with prenatal infection and social isolation simultaneously. Besides, all social isolated mice exhibited worse memory ability. Morphologically, the dendritic architecture of the granule cells in the dentate gyrus was examined. Reduced dendritic complexity and spine density were found in all experiment groups. Moreover, in Poly I:C offspring, more microglia were counted in hippocampus at P2 but not at P80, suggesting that the fetal immune system was transiently activated by prenatal infection. Finally, we assessed the density of GABAergic interneurons and oligodendrocytes by GAD67 and GST-π immunohistochemistry, respectively. There was no change found among all groups suggesting that prenatal infection and social isolation did not affect the number of GABAergic neurons and oligodendrocytes. Together, singular and synergistic effects of prenatal infection and social isolation on the structure and function of the dentate gyrus were noticed. The interplay of prenatal and postnatal environmental insults in relation to mental illness was demonstrated. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61602 |
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顯示於系所單位: | 解剖學暨細胞生物學科所 |
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