探討早期壓力及成年慢性不可預測壓力對恐懼社交轉移的影響;Investigate the effects of early life stress and adult chronic unpredictable stress on social transfer of fear

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Title:	探討早期壓力及成年慢性不可預測壓力對恐懼社交轉移的影響;Investigate the effects of early life stress and adult chronic unpredictable stress on social transfer of fear
Authors:	劉澤峋;Liu, Tze-Shiun
Contributors:	生命科學系
Keywords:	早期壓力;不可預知壓力;恐懼社交轉移;基底外側杏仁核;腹側海馬迴;前扣帶皮層;Early life stress;Chronic unpredictable stress;Social transfer of fear;Basolateral Amygdala;Ventral hippocampus;Anterior cingulate cortex
Date:	2023-07-19
Issue Date:	2024-09-19 15:20:02 (UTC+8)
Publisher:	國立中央大學
Abstract:	壓力為造成許多精神疾病的潛在因素。恐懼社交轉移(social transfer of fear)是一種透過觀察他人恐懼行為進而導致個體自身產生相同行為的學習過程，此學習能力不但提供個體自我保護機制，使個體未來在相似情境下能夠適應，此能力也是社交認知中重要的一環，當他人遭遇艱困情境時，個體能感同身受，並進一步做出利他的行為(例如: 安慰)。過去研究發現，許多精神疾病患者會有觀察性學習能力的缺陷，然而壓力是否影響恐懼社交轉移尚不清楚。個體從出生到成年皆可受到外在壓力的影響，為了探討不同年紀時遭受壓力是否會影響恐懼社交轉移，在本論文中，我們將壓力區分成幼年早期壓力(early life stress, ELS) 以及成年慢性不可預知壓力(chronic unpredictable stress, CUS)，並分成四組: 對照組(control)、早年壓力(ELS)、慢性不可預知壓力(CUS) 以及雙重壓力(double stresses, DS)，即早年壓力加上慢性不可預知壓力)。小鼠在出生後第二天開始接受為期13天的早期生活壓力)和/或在成年後接受為期14天的慢性不可預知壓力，結果發現有遭受慢性不可預知壓力的小鼠體重下降以及腎上腺重量增加，顯示慢性不可預知壓力確實對小鼠產生影響。在恐懼社交轉移中，我們讓上述四組的小鼠去觀察從未經歷過壓力(naïve)的陌生小鼠遭受電擊，並分析四組小鼠在觀察當下行為的表現。結果顯示雙重壓力的小鼠比對照組小鼠靜止不動的時間(freezing time)比只承受早期壓力或只承受了慢性壓力的小鼠更少，顯示雙重壓力小鼠無法感受並從陌生小鼠的情境中學習，在觀察性恐懼學習能力上有缺失的現象。我們更進一步去研究與恐懼社交轉移相關腦區的神經元活性，在恐懼社交轉移測試結束後，我們收取大腦組織並切片，利用免疫螢光染色技術以及c-Fos作為神經元的活性標記探討神經細胞被活化的情形，我們觀察到在慢性壓力組別小鼠在基底外側杏仁核(basolateral amygdala，BLA)中的LA被活化的c-Fos細胞的數量與對照組相比，有下降的趨勢。然而腹側海馬迴(ventral hippocampus，VHP)與前扣帶皮層(anterior cingulate cortex，ACC)在c-Fos數量上，卻沒有統計上的差異。根據上述結果顯示，壓力所引起的恐懼社交轉移損傷有一部分可能是與基底外側杏仁核的神經細胞失活(inactivation)有關。;Stress is a risk factor for many mental illnesses. Social transfer of fear is a learning process in which individuals observe fear-related behaviors in others and subsequently develop similar behaviors. This learning ability not only serves as a self-protective mechanism, making individuals to adapt to similar situations in the future, but also plays an important role in social cognition. When others experience distressing situations, individuals can empathize and engage in prosocial behaviors such as providing comfort. Previous studies have found deficits in observational learning abilities among individuals with various mental disorders. However, it remains unclear whether stress affects social transfer of fear. Individuals can experience external stressors throughout their lives, from infancy to adulthood. To investigate whether stress experienced at different ages influences social transfer of fear, this study divided stress into early life stress (ELS) and chronic unpredictable stress (CUS) in adulthood. Four groups were examined: a control group, early life stress (ELS) group, chronic unpredictable stress (CUS) group, and double stress (DS) group (i.e., both early life stress and chronic unpredictable stress). Mice were subjected to early life stress starting from the second day after birth for 13 days, and/or chronic unpredictable stress in adulthood for 14 days. We found that the mice decreased body weight and increased adrenal gland weight after CUS procedure, indicating the impact of CUS on mice. In the social transfer of fear, four groups of mice were placed in a chamber to observe a naïve stranger mouse receiving multiple electric shocks, and their behavioral responses during observation were be analyzed. The results showed that mice in the double stress group exhibited less freezing time (indicating fear response) compared to the ELS and CUS group, suggesting that these mice were unable to perceive and learn from the situation of the unfamiliar mouse, displaying deficits in observational fear learning abilities. Furthermore, we further investigated the neural activity in brain regions associated with social transfer of fear. After the social transfer of feat test, we collected brain for immunofluorescent staining. We used c-Fos as a marker for neuronal activity, to examine the activation of neurons in the basolateral amygdala (BLA), the ventral hippocampus (vHP), and the anterior cingulate cortex (ACC). We observed a decreasing trend in the number of activated c-Fos cells in basolateral amygdala in the CUS group compared to the control group. Collectively, this study suggests that the impairment of social transfer of caused by stress may be partially related to the inactivation of neurons in the basolateral amygdala.
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