研究生: |
羅子雅 Lo, Tsz-Nga |
---|---|
論文名稱: |
新生期投予地塞米松對於成年雌性大鼠 海馬迴 G 蛋白偶合雌激素受體之影響 Neonatal dexamethasone treatment attenuates hippocampal G-protein coupled estrogen receptor expression in adult female rat |
指導教授: |
呂國棟
Lu, Kwok-Tung |
學位類別: |
碩士 Master |
系所名稱: |
生命科學系 Department of Life Science |
論文出版年: | 2019 |
畢業學年度: | 107 |
語文別: | 英文 |
論文頁數: | 62 |
中文關鍵詞: | 地塞米松 、海馬迴 、G 蛋白偶合雌激素受體 、長期增益效應 |
英文關鍵詞: | G-protein coupled estrogen receptor, GPER |
DOI URL: | http://doi.org/10.6345/NTNU201900843 |
論文種類: | 學術論文 |
相關次數: | 點閱:43 下載:0 |
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Table of Contents
中文摘要 VI
ABSTRACT IX
INTRODUCTION 1
The long-term impact of early life adversities and traumatic experiences 1
The hypothalamic–pituitary–adrenal axis- 2
Estrogen Receptors and mental disorders 4
METERIALS AND METHODS 7
Animals 7
Neonatal Dexamethasone Administration Protocol 7
Somatic Growth Monitoring 8
Administration of G1, a Selective Agonist of G-protein Coupled Estrogen Receptor 8
Administration of G15, a Selective Antagonist of G-protein Coupled Estrogen Receptor 8
RESULTS 9
Neonatal Dexamethasone Treatment Lessen the Somatic Growth of Female Rats Temporarily 9
Neonatal Dexamethasone Treatment Promotes the Depression-like Behavior in the Adult Female Rats Demonstrated by Forced Swim Test 11
The NDT Induced Depression-like Behavior Demonstrated by Sucrose Preference Test 12
The Gene Expression of Hippocampal Gper was Decreased in NDT Adult Female Rats Analysed by Real-time Polymerase Chain Reaction 14
The Hippocampal LTP Formation was Decreased in NDT Adult Female Rats and Restored by Perfusion of GPER Agonist G1 and Blocked by Perfusion of GPER Antagonist G15 in NDT Adult Female Rats Analysed Using in vitro Electrophysiological Recording 16
DISCUSSION 19
FIGURES 26
Figure 1: The hypothalamic-pituitary-adrenal (HPA) axis response to the stress(Adapted from Raabe & Spengler, 2013). 26
Figure 2: The HPA axis plays a key role in the regulation homeostasis and the response to stress (Adapted from McGowan & Matthews, 2018). 27
Figure 3: The negative feedback control pathways of the glucocorticoids release (Adapted from Andrew J et al., Autopsy Pathology: A Manual and Atlas, 3th edition. Elsevier, 2016, ch.9). 28
Figure 4: Glucocorticoid signalling pathways (Adapted from Schoneveld et al., 2011). 29
Figure 5: Role of glucocorticoids in health and disease (Modified from Kadmiel & Cidlowski, 2013). 30
Figure 6: G-protein-coupled estrogen receptor (GPER) involved in regulation physiological responses and disease. (Modified from Prossnitz & Barton 2011). 31
Figure 7: The mechanisms of E2 in object recognition memory in ovariectomized mice. Adapted from (Adapted from Frick et al., 2018a). 32
Figure 8: Classical (genomic) and non-classical (non-genomic) mechanisms of E2 action (Adapted from Frick, 2015). 33
Figure 9: The Caveolin protein is responsible for the separation of functionally distinct signalling pathways in neurons (Adapted from Luoma et al., 2008). 34
Figure 10: Schematic representation of G-protein coupled estrogen receptor mediated signalling (Adapted from Liu et al., 2012). 35
Figure 11: Neonatal dexamethasone treatment impaired somatic growth of the female rats in a temporary manner. 36
Figure 12: Forced swim test for the depression-like behavior of NDT adult female rats. 37
Figure 13: Sucrose preference ratio for the depression-like behavior of NDT adult female rats. 38
Figure 14: Sucrose preference index for the depression-like behavior of NDT adult female rats. 40
Figure 15: qPCR Analysis on the Neonatal Dexamethasone Treatment Effect on the Hippocampal ERs Gene Expression in the Female Rats 41
Figure 16: GPER Agonist G1 Could Restore the High Frequency Stimulation- induced Hippocampal Long-term Potentiation in the Adult Female Rats. 42
Figure 16: GPER Agonist G1 Could Restore the High Frequency Stimulation- induced Hippocampal Long-term Potentiation in the Adult Female Rats. 43
Figure 17: GPER Antagonist G15 Could Blocked the GPER Agonist Effect on the High Frequency Stimulation-induced Hippocampal Long-term Potentiation in the Adult Female Rats. 45
Abbreviation table 46
References 50