|Alternative Title||Short- and long-term effects of social defeat stress on emotion and cognition in adolescent and adult mice|
|Place of Conferral||北京|
|Keyword||社会击败应激 青少期 社会交互 情绪 认知功能 抗抑郁药物|
|Abstract||青少期是参与情绪和认知功能调节的脑区和神经通路形成的重要阶段，也是社会性应激冲突最为明显的阶段。目前尚不清楚社会性应激如何影响青少期行为和脑的发育过程并对健康产生持续的影响。采用“居留者-入侵者”模型诱发社会击败应激，本研究比较了 10 天社会击败应激对青少期早期（PND2837），青少期后期（PND3847）和成年期（PND7079）小鼠情绪行为和认知功能的短时（应激结束后 1 天）和长时（应激结束后 6 周至成年期）影响，以考察应激对青少期行为发展的影响特征和应激敏感时间窗。 情绪行为检测包括社会交互和高架十字迷宫测试。采用注意定势转移任务评价包括信号鉴别学习，逆反学习和跨维度定势转移等多种认知功能。主要结果如下：|
首先，社会击败应激显著影响不同发育阶段小鼠的社会交互行为发展。动物在青少期晚期的社会交互行为多于青少期早期。 社会击败应激造成各年龄阶段动物明显的社会交互行为减少且在应激结束 6 周后持续表达。 同时青少期早期经历社会击败应激的小鼠成年后在高架十字迷宫测试中表现出更高的焦虑水平。
其次，社会击败应激对认知功能发展的影响存在发育阶段差异。在复杂信号系统中引入无关刺激时对青少期晚期动物的干扰明显高于成年动物。 社会击败应激造成成年期动物逆反学习能力短时损伤，但该影响在应激结束 6 周后恢复。应激并不影响青少期早期动物认知功能，但其成年后表现出逆反学习和跨维度定势转移能力损伤，尤其后者更为明显和稳定。社会击败应激未能诱发青少期晚期动物上述认知功能异常。 这些提示青少期早期是社会击败应激诱发跨维度定势转移能力持续改变的敏感阶段。
|Other Abstract||Adolescence is a key period during which the neural pathway regulating emotional and cognitive behaviors are established and social conflict emerges dramatically. However, how social stress during adolescence impacts on behavior and brain development which may result in enduring consequences for mental health remains unknown. In order to investigate how the stress differentially impacts behavior during critical windows throughout adolescent development, this study examined the short- (24h after the termination of stress) and long-term (6w after the termination of stress) effects of the repeated social defeat stress (SDS) using "resident-intruder" paradigm on emotional and cognitive behavior in early adolescent (PND 28-37, EA), late adolescent (PND 38-47, LA), and adult (PND70-79, ADULT) mice. The emotional behavioral tests include social interaction task (SIT) and elevated plus maze (EPM). Attentional set-shifting task (AST) was adopted to test the cognitive fucntion, including conditioning discrimination, reversal learning, and extra-dimentional set shifting. The main results as followed:|
Firstly, SDS resulted in distinctly different behavioral repertoires in adolescent compared to adult mice. Mice exhibited more social interaction during LA than EA. SDS significantly decreased social interaction in SIT across age groups, which persisted into adulthood. Furthermore, the adult mice subjected to social defeat stress during EA showed increased anxiety-like behavior in EPM test.
Secondly, SDS differently impacted on the development of cognitive function across different age group. LA mice were more susceptible to distraction than adult mice when an irrelevant stimulus dimension was introduced as part of a complex stimulus. SDS impaired the performance during reversal learning stage of AST in socially stressed adult mice, and this effect dissipated at 6w later. There was no effect of SDS on performance during each stage of AST in both stressed and control EA mice. However, when assessed during adulthood, stressed EA mice showed cognitive deficit during both reversal learning and extra-dimentional set-shifting stage in AST.
SDS failed to induce dysfunction of cognition in LA mice as both adolescents and adults. These suggested that EA might be a sensitive stage during which (SDS) resulted in adult dysfunction of cognitive flexibility.
Thirdly, chronic treatment with antidepressant duloxetine reversed the decreased social interaction, the increased anxiety-like behaviors, and the impairment of cognitive function in adults experiencing SDS during EA.
Thus, SDS produced different behavioral patterns depending on the developmental stage exposure to stress, suggesting EA might be a critical window during which SDS induced the alterations of emotion and cortically mediated cognitive function during adulthood.
|原三娜. 社会击败应激对青少期和成年期小鼠情绪与认知功能 的短时和长时影响[D]. 北京. 中国科学院研究生院,2013.|
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