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系統識別號 U0026-2707201813510100
論文名稱(中文) 探討陪伴小鼠的健康或社交傾向及數量對於壓力誘使海馬齒狀回中細胞增生以及神經母細胞增生的數量降低之影響
論文名稱(英文) Impact of group housing quantity and quality on the stress-induced decreases in the number of dentate newly proliferated cells and neuroblasts
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 106
學期 2
出版年 107
研究生(中文) 孫莉涵
研究生(英文) Li-Han Sun
學號 S36051027
學位類別 碩士
語文別 中文
論文頁數 39頁
口試委員 指導教授-游一龍
口試委員-謝坤叡
口試委員-康宏佑
口試委員-楊尚訓
中文關鍵字 壓力  海馬齒狀回  陪伴  早期神經發生  催產素 
英文關鍵字 Stress  Dentate gyrus  Companion  Early neurogenesis  Oxytocin 
學科別分類
中文摘要 為了維護個人的身體或心理健康,利用各種形式去獲得社會支持是相當重要的。許多研究也發現社交障礙會與個人主觀的生活品質下降以及精神狀態的耗竭程度有關。在實驗室先前的研究已顯示,給予小鼠串聯壓力(不可預期的足部電擊繼之以水中禁錮) 可以快速且有效地降低小鼠海馬齒狀回(DG)中細胞增生和早期神經新生的數量,若在受壓力的同時給予三隻同種同伴陪伴,可以減緩或完全免除這個下降的趨勢。本研究宗旨在延伸過去的發現,探討接受壓力的實驗小鼠和其陪伴小鼠間肢體接觸的有無,以及陪伴小鼠的健康或社交傾向品質和數量是否會改變上述的減緩效果。首先,為了預防肢體接觸,在本研究中的壓力模式採取一小時的水中禁錮,比較一隻同種同伴者施打單一劑生理食鹽水、催產素(OT)或三隻同種同伴者施打單一劑脂多醣(LPS)以及棉花尖端浸漬OT的壓力減緩效果為何。結果指出,一小時的水中禁錮和串連壓力在造成細胞增生及早期神經新生的下降效果幾乎一樣,而三隻陪伴小鼠的緩衝效果也類似,所以實驗小鼠和陪伴小鼠的身體接觸或因壓力所產生的攻擊行為都不是影響的因素。接著我們發現三隻沒做任何處理的同性別陪伴小鼠和施打LPS的同種陪伴小鼠都得以在雄性實驗小鼠身上阻止壓力誘使DG中新增生的細胞和神經母細胞數量減少的情形。有趣的是,這三隻同種陪伴小鼠的這些壓力減緩效果並不影響壓力造成皮質酮(CORT)上升的現象,而一隻施打生理食鹽水以及OT(1 mg / kg)的陪伴小鼠則沒有發出有效的壓力減緩效果。另外,我們發現藉由空氣傳播的OT可以成功阻止壓力誘使DG中細胞增生和早期神經新生降低的情形,而使用對實驗小鼠周邊OT受體產生阻斷訊息傳遞的拮抗劑 (L-371,257) 則可以消除這樣的減緩效果。這些結果促使我作以下的結論,第一,陪伴小鼠的肢體接觸和身體健康狀況似乎對於壓力造成DG中新增生的細胞和早期神經新生數量下降,以及壓力誘導的CORT上升較沒有影響。第二,陪伴小鼠在本模型中的壓力緩衝效果是確定存在的,但一隻陪伴小鼠似乎無法有此效果。最後,空氣中的OT可能是透過刺激周邊的OT受體去扮演著壓力緩衝的角色。關於OT影響DG的細胞增生以及早期神經新生的議題值得再加以探討,或許在未來可以替代在壓力下同伴陪伴的效果。
英文摘要 To obtain various forms of social support is critical for maintaining individual’s psychological and physical well-being. Social interaction impairments have been frequently associated with decreased quality of life and psychopathological states. Previously, we have reported that the presence of three conspecifics prevents contact-involving stressors-induced decreases in newly proliferated cell and neuroblast in mouse hippocampal dentate gyrus (DG). This study was designed to determine whether physical interaction, number of conspecifics, and conspecifics’ physiological status were important in the emergence of these stress-buffering effects. To avoid physical interaction, here a 1-hr contact-free stressor regiment consisting of restraint in water was used. Although the unconditioned footshock stressor was smitted, the contact-free single stressor regimen induced comparable decreases in DG cell proliferation and early neurogenesis as compared to the original compound stressors. In this regard, the presence of one saline-, oxytocin (OT)-pretreated, or three lipopolysaccharide (LPS)-pretreated conspecifics and cotton tip-impregnated with OT were assessed for the buffering effects. We found that presentation of three intact and LPS-pretreated conspecifics prevented the stressor-induced decreases in the number of newly proliferated cell and neuroblast in hippocampal DG, while three conspecifics did not affect the stressor-stimulated corticosterone (CORT) elevations. Presentation of one saline- or OT (1 mg/kg)-pretreated conspecific did not exert observable stress-buffering effects. Airborne OT was found to prevent the stressor-induced decreases in DG cell proliferation and early neurogenesis, while pretreatment with a selective peripheral OT receptor antagonist, L-371,257, abolished such OT-produced buffering effects, no matter using intraperitoneal injection or nasal cavity lavage. These findings, taken together, suggest that conspecifics’ physical interaction and sickness play a minor role in mediating the conspecifics’ buffering effects on stress-induced decreases in cell proliferation, early neurogenesis or stress-provoked CORT secretion. Moreover, stress-buffering effects are eminent with the presence of three conspecifics but negligible with presentation of one. Finally, airborne OT produces stress-buffering effects in this regard possibly via its stimulation on peripheral OT receptors. OT merits further study to substitute for companions’ stress-buffering effects in this regard.
論文目次 Abstract (Chinese) -------------------------------------1
Abstract (English) -------------------------------------3
Introduction
1. Stress and neurogenesis in hippocampal dentate gyrus --------------------------------------------------8
2. Companion effect -------------------------------9
3. Oxytocin --------------------------------------10
Materials and Methods
1. Animals ---------------------------------------12
2. The Stressor Regimens -------------------------12
3. Grouping and the Experimental Procedures ------13
4. Immunohistochemical Staining Protocol ---------15
5. Quantification of Newly Proliferated Cells and Neuroblasts in DG -------------------------------------16
6. Serum CORT concentration ----------------------16
7. Statistical analysis --------------------------17
Results
1. The presence of three conspecifics prevented the compound and single stressor regimen-induced decreases in the number of newly proliferated cells and neuroblasts in DG ----------------------------------------------------18
2. Neither the compound stressors nor the presence of three conspecifics affected the survival of newly proliferated cell or proliferative neuroblast in DG ---18
3. The presence of three saline- and LPS-pretreated conspecifics, while not one saline- or OT-pretreated conspecific, prevented the single stressor-induced decreases in new cell proliferation and early neurogenesis in DG ------------------------------------18
4. Airborne OT exposure prevented the single stressor regimen-induced decreases in new cell proliferation and early neurogenesis in DG possibly through OT stimulation on peripheral OT receptor ------19
Discussion --------------------------------------------20
References --------------------------------------------24
Figure Legend
Figure 1. The timelines of the experimental procedures-30
Figure 2. Photo representatives -----------------------32
Figure 3. The effects of the stressor regimens and the presence of three conspecifics on the number of newly proliferated cell (BrdU-staining spot), proliferative neuroblast (BrdU/DCX-staining spot) and serum corticosterone (CORT) level ---------------------------33
Figure 4. The effects of the compound stressor regimen (30-min unconditioned foot shocks immediately followed by 30-min restraint and immersed in water) and the presence of three conspecifics on the survival of the BrdU-labelled cells and neurblasts in dentate gyrus over a 7-day period --------------------------------------------35
Figure 5. The effects of the number (one vs. three) of conspecifics, the sickness of the housing conspecifics, and oxytocin-pretreated conspecifics on the single stressor regimen-induced decreases in newly proliferated cell and neuroblast in dentate gyrus ------------------36
Figure 6. Effects of airborne oxytocin (OT) and L-368,899 i.p.-pretreatment on the single stressor regimen-induced decreases in the number of newly proliferated cell and proliferative neuroblast in dentate gyrus -------------37
Figure 7. Effects of airborne oxytocin (OT) and L-371,257 lavage-pretreatment on the single stressor regimen-induced decreases in the number of newly proliferated cell and proliferative neuroblast in dentate gyrus and increases in serum corticosterone (CORT) levels -------38
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