Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders
Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders
复制标题
DOI：
10.1017/s1461145710001239
复制
发表时间：
2011-05-01
影响因子：
4.8
通讯作者：
Nabeshima, Toshitaka
中科院分区：
文献类型：
--
作者：
Niwa, Minae;Matsumoto, Yurie;Nabeshima, Toshitaka
生命早期的不良事件，包括母亲分离和社会隔离，深刻影响大脑发育和成年行为，并可能导致遗传易感个体发生精神疾病，如精神分裂症和情绪障碍。这些环境诱导的发育适应的分子机制尚不清楚，最好在动物范式与翻译显着性评估。在这项研究中，我们检查了出生后15至21天之间母亲分离和/或社会隔离6小时/天的小鼠在成年期在旷场，社会互动，高架十字迷宫，强迫游泳，Y迷宫，新物体识别，条件性恐惧学习，前脉冲抑制和运动活动测试中的表现的影响，以研究这种动物模型是否可以显示精神分裂症和情绪障碍的表型。母亲分离和隔离的压力导致成年人的行为缺陷，下丘脑-垂体-肾上腺轴的激活，额叶皮质中去甲肾上腺素和多巴胺的水平以及杏仁核中多巴胺和5-羟色胺的代谢物的水平降低，表明行为缺陷涉及内分泌和神经元风险。结果表明，额叶皮层和杏仁核经历了由母亲分离和隔离的压力引起的结构重塑，这改变了成年后的行为和生理反应，包括焦虑，记忆和其他认知过程。此外，社会隔离加剧了由母亲分离引起的行为功能障碍。这些研究结果表明，母亲分离和生命早期的社会孤立可能导致长期的异常行为和病理生理损伤，包括精神分裂症和情绪障碍。
Adverse events early in life, including maternal separation and social isolation, profoundly affect brain development and adult behaviour and may contribute to the occurrence of psychiatric disorders such as schizophrenia and mood disorders in genetically predisposed individuals. The molecular mechanisms underlying these environmentally induced developmental adaptations are unclear and best evaluated in animal paradigms with translational salience. In this study, we examined the effects in mice of maternal separation and/or social isolation for 6 h/d between postnatal days 15 and 21 on performance during adulthood in the open-field, social interaction, elevated plus-maze, forced swimming, Y-maze, novel object recognition, conditioned fear-learning, prepulse inhibition, and locomotor activity tests, to investigate whether this animal model could show the phenotypes for schizophrenia and mood disorders. The stress of maternal separation and isolation led to adult behavioural deficits, activation of the hypothalamic-pituitary- adrenal axis, and decreases in the levels of norepinephrine and dopamine in the frontal cortex and metabolites of dopamine and serotonin in the amygdala, showing the involvement of endocrine and neuronal risk in behavioural deficits. The results suggest that the frontal cortex and amygdala undergo structural remodelling induced by the stress of maternal separation and isolation, which alters behavioural and physiological responses in adulthood, including anxiety, memory and other cognitive processes. Further, social isolation enhanced the behavioural dysfunctions induced by maternal separation. These findings indicate that maternal separation and social isolation early in life can lead to long-lasting abnormal behaviour and pathophysiological impairments including schizophrenia and mood disorders.