請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60729完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賴文崧 | |
| dc.contributor.author | Ju-Chun Pei | en |
| dc.contributor.author | 裴如淳 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:27:45Z | - |
| dc.date.available | 2018-08-20 | |
| dc.date.copyright | 2013-08-20 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-15 | |
| dc.identifier.citation | Chapter 1
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Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacology & Therapeutics, 122, 150-20 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60729 | - |
| dc.description.abstract | 精神分裂症為一盛行率達 1%、造成認知缺損且遺傳性高之心理疾病。苦於致病機轉不明，在治療病人認知缺損症狀上始終效果不佳。故本研究主題為精神分裂症相關基因neuregulin 1(Nrg1)之致病機轉。多項研究指出Nrg1與海馬迴神經可塑性有關，其可能為導致精神分裂症病人認知缺損之病因。本研究利用Nrg1缺損小鼠，欲透過觀察認知行為表現，配合藥物操弄、神經型態研究、神經傳導物質表現量等多取向的實驗設計，來深入探討精神分裂症的認知缺損機轉。實驗一，欲分析基因對於不同性別之多項行為表現影響，著重於觀察此基因對於與學習記憶之影響。實驗發現Nrg1缺損會造成認知作業缺損，特別是在公鼠身上。而，兩個月和六個月大的Nrg1缺損小鼠在基礎行為測試表現正常，此可排除導致認知能力不佳之混淆變項。實驗二測試較易受到影響之神經傳導系統，觀察施打藥物後引發之行為反應。結果顯示Nrg1缺損公鼠之GABA神經傳導系統較脆弱。實驗三進一步觀察海馬迴之神經型態與GABA神經傳導物質表現量。Nrg1缺損小鼠雖無明顯地神經細胞型態改變，但在Nrg1缺損公鼠海馬迴的GABA中介神經元表現明顯低落。實驗四進一步使用 GABA相關抗癲癇藥-丙戊酸鈉(Valproate)，成功扭轉其在認知作業上的缺損，以期提供病人藥物治療之發展方向。 | zh_TW |
| dc.description.abstract | Accumulating evidence from human and animal studies suggest that neuregulin 1 (Nrg1) might be involved in the neurodevelopment, GABAergic neurotransmission, and pathogenesis of schizophrenia. Nrg1 belongs to the neuregulin family of growth factors and its expression has been found in many brain regions, especially in the hippocampus. Emerging studies start to reveal that Nrg1 signaling is related to the neural plasticity which might be responsible for the cognitive deficits in schizophrenic patients. To determine the involvement of Nrg1 in cognitive functions and the importance of Nrg1 in the regulation of neuromorphology and neurochemicals in vivo, a new line of Nrg1 mice that carry a truncation of transmembrane (TMc) domain of Nrg1 from exon 9 were generated and used in this study. Both male and female TMc domain-Nrg1+/- mutant mice and their wild-type littermates were used in a series of 4 experiments. In Experiment 1, a comprehensive battery of cognitive-related tasks and basic behavioral tasks was applied to evaluate the behavioral phenotypes of our Nrg1+/- mutant mice. Nrg1+/- mice exhibited a normal profile of basic function but significant impairments in their cognitive functions, especially in males. Experiments 2 and 3 were conducted to reveal conceivable clues for interpreting the observed behavioral deficits. In Experiment 2, pharmacological challenges were conducted. Both males and females received an acute administration of MK-801, methamphetamine, and pentylenetetrazol, respectively. Our data indicated that the injection of PTZ induced significant behavioral alterations in male (but not female) Nrg1+/– mice whereas the other two drugs had no effect, suggesting a potential alteration of GABAergic activity in the brain of mutant males. Neuromorphological and neurochemical alterations in the hippocampus of mutant mice were further examined in Experiment 3, respectively. Neuromorphometric analysis of pyramidal neurons in the CA1 region of hippocampus in these mice revealed that no significant morphological alteration was found. However, a significant reduction of GAD67 and parvalbumin expression level was found in the hippocampus of Nrg1+/– mutant males but not in females. In Experiment 4, we found that the use of valproate, a GABA-related pharmacoepigenomic, successfully rescued observed cognitive deficits in male Nrg1+/– mutant mice. Collectively, these results indicate the importance of Nrg1 in the regulation of hippocampus-related cognitive functions and the expression of hippocampal GABAergic interneurons, especially in males. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:27:45Z (GMT). No. of bitstreams: 1 ntu-102-R98227126-1.pdf: 5202403 bytes, checksum: 32250947821142d3b23531875b6f27d5 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 致謝 i
摘要 iii Abstract v Table of Contents vii Figures and Tables ix Chapter 1 General Introduction 1 1. Overview of schizophrenia 1 2. The neurochemistry of schizophrenia 4 3. The etiology of schizophrenia 13 4. What is neuregulin 1 (NRG1)? 15 5. Using genetically engineered animal models to study the role of Nrg1 in the pathogenesis of schizophrenia 24 6. The objective of this study 33 References 39 Chapter 2 Sex- Specific Alteration of Cognitive Function and the Expression of GABAergic Interneurons in Hippocampus of Neuregulin 1 Deficient Mice 65 Introduction 65 Materials and Methods 70 Results 87 Discussion 91 References 120 Chapter 3 General Discussion 139 Nrg1 and the dysregulation of LTP 139 GABA hypothesis of schizophrenia as a primary etiology of schizophrenia 140 Nrg1 modulates sex-specific alteration on GABAergic transmission 142 The epigenetic processes of valproate in Nrg1 mutant 143 The foundation of “second hit”: Nrg1 deficit plays a critical role in interacting with environmental insults 144 All roads lead to common pathway? Different genetic alteration leads to diversity of clinical symptoms of schizophrenia 147 Rethinking biological psychiatry: Nrg1 polymorphisms may confer a wider susceptibility of psychiatric illness 148 References 150 Appendix 159 | |
| dc.language.iso | en | |
| dc.subject | 認知作業 | zh_TW |
| dc.subject | 神經形態學 | zh_TW |
| dc.subject | 精神分裂症 | zh_TW |
| dc.subject | Nrg1 | zh_TW |
| dc.subject | 丙戊酸鈉 | zh_TW |
| dc.subject | 行為表現型 | zh_TW |
| dc.subject | GABA 中介神經元 | zh_TW |
| dc.subject | Nrg1 | en |
| dc.subject | schizophrenia | en |
| dc.subject | valproate | en |
| dc.subject | GABAergic interneuron | en |
| dc.subject | pentylenetetrazol | en |
| dc.subject | neuromorphology | en |
| dc.subject | behavioral phenotyping | en |
| dc.title | 以精神分裂症候選基因Nrg1缺損小鼠為模型－檢驗Nrg1調控海馬迴相關認知作業與海馬迴GABA中介神經元表現之效果 | zh_TW |
| dc.title | Examination of the Sex-Specific Effect of Nrg1, a Candidate Gene for Schizophrenia, in the Regulation of Hippocampal Cognitive Functions and the Expression of Hippocampal GABAergic Interneurons – Using Neuregulin 1 Deficient Mice as a Model | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李立仁,梁庚辰,劉怡均,劉智民 | |
| dc.subject.keyword | 精神分裂症,Nrg1,行為表現型,認知作業,神經形態學,GABA 中介神經元,丙戊酸鈉, | zh_TW |
| dc.subject.keyword | schizophrenia,Nrg1,behavioral phenotyping,neuromorphology,pentylenetetrazol,GABAergic interneuron,valproate, | en |
| dc.relation.page | 163 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-15 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 心理學研究所 | zh_TW |
| 顯示於系所單位： | 心理學系 | |
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