成年神經新生發生於腦中兩個腦區：側腦室中旁區及海馬迴齒狀迴內側區，海馬迴齒狀迴內側區的新生神經與新記憶的形成有相當大的關係。氧化壓力所造成的ＤＮＡ損傷會使鹼基異常進而影響細胞增生、細胞分化或導致細胞死亡，這類因氧化壓力所造成的DNA損傷大部分由鹼基去除修復機制來修正錯誤的鹼基，鹼基去除修復機制中有許多酵素參與，DNA糖基化酶參與了修復步驟中的第一步，也就是辨認並去除錯誤的鹼基，因此當沒有DNA糖基化酶的表現時會造成氧化性損傷的DNA累積，DNA糖基化酶包含許多種類而我們感興趣的是NEIL1，NEIL1在整個腦中都有豐富的表現其中也包含了海馬迴，我們認為NEIL1可以維持在成年神經新生的過程中細胞生長的穩定，因此我們假設當NEIL1缺少時會影響新生神經的細胞增生或分化進而導致學習記憶上的損傷，我們使用NEIL1剔除小鼠作為實驗動物，首先我們發現NEIL1剔除小鼠在神經新生數量較少，但是神經分化的程度不受影響，在培養的神經祖細胞實驗中得知，NEIL1剔除胚胎鼠細胞增生的程度不受影響，然而我們藉由不同時間點來觀察神經新生的數量後發現NEIL1剔除小鼠的新生細胞較容易死亡，同時NEIL1剔除小鼠在空間記憶及數短期記憶能力也有損傷，氧化性DNA損傷累積所影響的範圍廣泛且還有許多未知，我們試著找出什麼原因使在NEIL1剔除小鼠的新生細胞容易死亡，我們從參與細胞生長存活與死亡相關的路徑分子探討，發現在NEIL1 剔除小鼠中參與細胞存活的分子β-catenin 和跟內質網壓力相關的IRE1α mRNA表現量下降，而參與細胞死亡的分子p53和抗氧化基因GCLC、GCLM的表現量上升，從我們的結果可以知道DNA糖基化酶NEIL1對成年神經新生的重要且提出一些可能受NEIL1所影響的機制。

Adult neurogenesis is spatially restricted to two brain regions, the subventricular zone of the lateral ventricles and subgranular zone in the dentate gyrus of the hippocampus. Efficient memory formation has been reported to rely on adult neurogenesis in the SGZ of the hippocampus. Several types of DNA damage including modifications to DNA bases raised from oxidative stress are a significant threat to the genome stability of neural progenitor cells. The accumulation of oxidative DNA damages might affect cell proliferation, differentiation or lead to cell apoptosis. This type damage is mostly repaired by base excision repair. DNA glycosylase participates in the critical step of base excision repair to recognize and remove the damaged bases. We are interested to functionally characterize the importance of Endonuclease VIII-like 1 (NEIL1), one kind of DNA glycosylase, in adult hippocampal neurogenesis. Hence, we hypothesized that NEIL1 deficiency might suppress the adult hippocampal neurogenesis which is resulted from the abnormalities of cell proliferation and differentiation. Using in vivo NEIL1 deficiency (NEIL1-/-) mice to monitor cell proliferation and differentiation of adult neurogenesis in the subgranular zone with labeling BrdU and doublecortin, an immature neuron marker. There were less newborn neurons in NEIL1-/- than wild-type (WT) mice. However, the ratio of how many newborn cells differentiated into neurons was not affect by NEIL1 deficient. We further investigated that the NEIL1-/- mice reduce adult neurogenesis due to insufficient cell proliferation or the impaired survival of newly proliferated immature neurons. We observed the neurogenesis processes by examining the adult neurogenesis on 1, 3 or 5 days BrdU labeling. We found that the decreased neurogenesis in the NEIL1-/- mice results from the impaired survival of newly proliferated neurons. The results of embryonic neurospheres proliferation assay also supported that cell proliferation is not affected by the NEIL1 deficiency. Moreover, the NEIL1 deficiency impaired the spatial and non-spatial hippocampus-related memory functions with Y-maze spontaneous alternation test and novel object recognition test, respectively. To investigate the underlying mechanisms, we analyzed the molecules which participate in cell survival and apoptosis. We found that NEIL1 deficiency mice downregulated the mRNA level of β-catenin, a key molecule involved in cell survival, and the ER stress sensor: IRE1α. Also, the intensities of p53, the critical controller of apoptosis process, was upregulated by NEIL1 deficient. Besides, the antioxidant genes: GCLC and GCLM were increased in NEIL1 deficient mice. In this study, we proved the importance of NEIL1 in adult neurogenesis and provided some possible mechanisms which might involve in the regulation of NEIL1 in adult neurogenesis.

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