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題名 成年大鼠海馬迴之新生成神經細胞在學習記憶中所扮演的角色
The role of adult born neurons of the hippocampus in learning and memory
作者 林曉涵
Lin, Hsiao Han
貢獻者 賴桂珍
Lai, Guey Jen
林曉涵
Lin, Hsiao Han
關鍵詞 海馬迴
學習與記憶
神經新生
Hippocampus
Learning and Memory
Neurogenesis
日期 2013
上傳時間 3-Mar-2014 15:41:13 (UTC+8)
摘要 海馬迴為主要參與學習記憶和認知的腦區，許多認知功能異常與海馬迴有關，例如阿茲海默症、壓力皆會對認知功能造成影響。在成熟哺乳類動物的大腦中發現海馬迴的顆粒細胞下區(Subgranular zone, SGZ)持續有新神經細胞生成。在先前的實驗，我們在海馬迴之顆粒細胞大量死亡的大鼠中成功促進成體神經新生（adult neurogenesis）而且使海馬迴的學習記憶功能恢復，但對於這些新生成神經細胞是否參與學習記憶的進行並不清楚。海馬迴的顆粒細胞需要腎上腺所分泌的皮質酮才能生存，如果將雙側腎上腺移除會造成顆粒細胞大量死亡。因此摘除雙側腎上腺（adrenalectomized,ADX）的老鼠可以當作一個研究海馬迴之顆粒細胞死亡與新生的模型。當ADX三個月後給予sonic hedgehog(shh)和豐富環境後，觀察到有大量的新顆粒細胞生成，而且原本有問題的海馬迴之學習記憶功能也恢復正常。所以接下來我們要探討這些新生成的神經細胞是否併入原本的神經網絡，而且參與學習記憶的過程，利用Arc的組織免疫染色來觀察，Arc屬於當突觸活化時會立即表達的基因（immediate early gene），在進行行為測試後1.5小時可被觀察到。以觀察Arc和BrdU（標定十週前所新生成的細胞）共同染到的狀況，推測新生成神經細胞參與在學習記憶上。從我們的實驗結果顯示給予Shh後待豐富環境的ADX老鼠比待一般鼠籠環境的ADX老鼠在齒狀迴有大量的Arc和BrdU共同被染到，而且在Object-context association行為測試上，待豐富環境的老鼠，表現與正常老鼠一樣，但是待一般鼠籠環境的則與沒給Shh處理的ADX老鼠表現相同，顯示Shh的治療效果必須搭配豐富環境才能顯現出來。從結果推測經過Shh和豐富環境刺激所生成且存活下來的神經細胞會參與在神經網絡的活動中。
The hippocampus is a brain region critical to learning and memory and is a frequent target of many neurological diseases such as Alzheimer’s, other forms of dementia, and chronic stress that have dramatic cognitive consequences. The Subgranular zone (SGZ) of the hippocampus is one of the mammalian brain regions where new neurons are generated continuously throughout adult life. Previously, we have successfully promoted adult neurogenesis and demonstrated functional recovery after hippocampal granule cell degeneration in a rat model.
This study was undertaken to address the question of whether the adult-born neurons were integrated into a neural network and involved in the process of learning and memory. Corticosterone, secreted by adrenal glands, is required for hippocampal granule cell survival and bilateral removal of adrenal glands lead to granule cell death. Therefore, adrenalectomized (ADX) rats were used to ablate, and regenerate granule cells in the hippocampus. Three months after treatment of ADX animals with sonic hedgehog (shh) and environmental enrichment, significant amount of granule cell regeneration and restoration of brain function was observed. To determine whether the new born neurons were integrated into a neural network and participated in the learning and memory process, immunohistochemistry for Arc, a synaptic activity dependent immediate early gene product was performed after behavior test. Colocalization of Arc and BrdU (a marker for neurons born 10 weeks ago) staining suggests that new neurons which were born during shh treatment were involved in the learning and memory. Colocalization of Arc and BrdU was more abundant in the dentate gyrus of the hippocampus in ADX animals treated with shh and housed in the enriched environment when compared with untreated ADX animals or ADX animals treated with shh but housed in cages. These results suggest that after treatment with shh and environmental enrichment, new born neurons survives for at least 3 months and participates in the activities of neural networks.
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描述 碩士
國立政治大學
神經科學研究所
99754004
102
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0099754004
資料類型 thesis
dc.contributor.advisor 賴桂珍zh_TW
dc.contributor.advisor Lai, Guey Jenen_US
dc.contributor.author (Authors) 林曉涵zh_TW
dc.contributor.author (Authors) Lin, Hsiao Hanen_US
dc.creator (作者) 林曉涵zh_TW
dc.creator (作者) Lin, Hsiao Hanen_US
dc.date (日期) 2013en_US
dc.date.accessioned 3-Mar-2014 15:41:13 (UTC+8)-
dc.date.available 3-Mar-2014 15:41:13 (UTC+8)-
dc.date.issued (上傳時間) 3-Mar-2014 15:41:13 (UTC+8)-
dc.identifier (Other Identifiers) G0099754004en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/64383-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 神經科學研究所zh_TW
dc.description (描述) 99754004zh_TW
dc.description (描述) 102zh_TW
dc.description.abstract (摘要) 海馬迴為主要參與學習記憶和認知的腦區，許多認知功能異常與海馬迴有關，例如阿茲海默症、壓力皆會對認知功能造成影響。在成熟哺乳類動物的大腦中發現海馬迴的顆粒細胞下區(Subgranular zone, SGZ)持續有新神經細胞生成。在先前的實驗，我們在海馬迴之顆粒細胞大量死亡的大鼠中成功促進成體神經新生（adult neurogenesis）而且使海馬迴的學習記憶功能恢復，但對於這些新生成神經細胞是否參與學習記憶的進行並不清楚。海馬迴的顆粒細胞需要腎上腺所分泌的皮質酮才能生存，如果將雙側腎上腺移除會造成顆粒細胞大量死亡。因此摘除雙側腎上腺（adrenalectomized,ADX）的老鼠可以當作一個研究海馬迴之顆粒細胞死亡與新生的模型。當ADX三個月後給予sonic hedgehog(shh)和豐富環境後，觀察到有大量的新顆粒細胞生成，而且原本有問題的海馬迴之學習記憶功能也恢復正常。所以接下來我們要探討這些新生成的神經細胞是否併入原本的神經網絡，而且參與學習記憶的過程，利用Arc的組織免疫染色來觀察，Arc屬於當突觸活化時會立即表達的基因（immediate early gene），在進行行為測試後1.5小時可被觀察到。以觀察Arc和BrdU（標定十週前所新生成的細胞）共同染到的狀況，推測新生成神經細胞參與在學習記憶上。從我們的實驗結果顯示給予Shh後待豐富環境的ADX老鼠比待一般鼠籠環境的ADX老鼠在齒狀迴有大量的Arc和BrdU共同被染到，而且在Object-context association行為測試上，待豐富環境的老鼠，表現與正常老鼠一樣，但是待一般鼠籠環境的則與沒給Shh處理的ADX老鼠表現相同，顯示Shh的治療效果必須搭配豐富環境才能顯現出來。從結果推測經過Shh和豐富環境刺激所生成且存活下來的神經細胞會參與在神經網絡的活動中。zh_TW
dc.description.abstract (摘要) The hippocampus is a brain region critical to learning and memory and is a frequent target of many neurological diseases such as Alzheimer’s, other forms of dementia, and chronic stress that have dramatic cognitive consequences. The Subgranular zone (SGZ) of the hippocampus is one of the mammalian brain regions where new neurons are generated continuously throughout adult life. Previously, we have successfully promoted adult neurogenesis and demonstrated functional recovery after hippocampal granule cell degeneration in a rat model.
This study was undertaken to address the question of whether the adult-born neurons were integrated into a neural network and involved in the process of learning and memory. Corticosterone, secreted by adrenal glands, is required for hippocampal granule cell survival and bilateral removal of adrenal glands lead to granule cell death. Therefore, adrenalectomized (ADX) rats were used to ablate, and regenerate granule cells in the hippocampus. Three months after treatment of ADX animals with sonic hedgehog (shh) and environmental enrichment, significant amount of granule cell regeneration and restoration of brain function was observed. To determine whether the new born neurons were integrated into a neural network and participated in the learning and memory process, immunohistochemistry for Arc, a synaptic activity dependent immediate early gene product was performed after behavior test. Colocalization of Arc and BrdU (a marker for neurons born 10 weeks ago) staining suggests that new neurons which were born during shh treatment were involved in the learning and memory. Colocalization of Arc and BrdU was more abundant in the dentate gyrus of the hippocampus in ADX animals treated with shh and housed in the enriched environment when compared with untreated ADX animals or ADX animals treated with shh but housed in cages. These results suggest that after treatment with shh and environmental enrichment, new born neurons survives for at least 3 months and participates in the activities of neural networks.		en_US
dc.description.tableofcontents 中文摘要...Ⅰ
英文摘要...Ⅱ
目錄...Ⅲ
第一章、 緒論...1
第一節、 海馬迴（Hippocampus）...1
1. 海馬迴的構造...1
2. 海馬迴的訊號傳遞...1
3. 海馬迴與學習記憶...2
4. 齒狀迴的功能...4
5. 海馬迴相關的學習記憶行為實驗...4
第二節、 成體神經新生（Adult Neurogenesis）與調控...5
1. 成體神經新生...5
2. 調控神經新生...7
3. Sonic hedgehog促進神經新生...8
4. 豐富環境（Environmental enrichment, EE）促使新生成神經細胞生存...9
第三節、 上腺摘除手術(Adrenalectomy)引發海馬迴顆粒細胞死亡...10
1. 腎上腺(Adrenal gland)...10
2. 下視丘-腦垂腺-腎上腺軸(Hypothalamic-Pituitary-Adrenal, Axis)...10
3. 腎上腺摘除手術(Adrenalectomy)...11
第四節、 運用立即表現基因(immediate-early gene, IEG)觀察活化神經細胞...12
1. 立即表現基因...12
2. Arc基因影響學習記憶...13
第五節、 本論文實驗目的及策略...14
第二章、 實驗材料方法...15
1. 實驗動物...15
2. 腎上腺摘除手術（Adrenalectomy）...15
3. 在手術前一天準備埋管的材料...16
4. 立體定位手術（Stereotaxic surgery）與埋管...17
5. 埋管後飼養環境...18
6. 給予Corticosterone（CORT）...18
7. 行為測試-物品與情境聯合試驗（Object-context association）...19
8. 腦組織的灌流製備與切片...20
9. 腦組織染色(Immunohistochemistry,IHC)...21
10. 切片細胞計數分析軟體...22
11. 行為結果分析...22
12. 統計分析...22
13. 實驗流程圖...23
第三章、 結果...24
1. 摘除腎上腺後體重變化...24
2. 摘除腎上腺後ADX與Sham細胞數比較...26
3. Shh與豐富環境恢復ADX老鼠之學習記憶能力...28
4. 新生成神經細胞參與學習記憶行為...30
（1） 新生成細胞比較...30
（2） 新生成神經細胞參與行為...32
（3） 成熟之新生成神經細胞大量活化...36
a. 成熟之新生成神經細胞...36
b. 未成熟之新生成神經細胞...42
第四章、 討論...46
第五章、 結論...49
參考文獻...50		zh_TW
dc.format.extent 1889732 bytes-
dc.format.mimetype application/pdf-
dc.language.iso en_US-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0099754004en_US
dc.subject (關鍵詞) 海馬迴zh_TW
dc.subject (關鍵詞) 學習與記憶zh_TW
dc.subject (關鍵詞) 神經新生zh_TW
dc.subject (關鍵詞) Hippocampusen_US
dc.subject (關鍵詞) Learning and Memoryen_US
dc.subject (關鍵詞) Neurogenesisen_US
dc.title (題名) 成年大鼠海馬迴之新生成神經細胞在學習記憶中所扮演的角色zh_TW
dc.title (題名) The role of adult born neurons of the hippocampus in learning and memoryen_US
dc.type (資料類型) thesisen
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