Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice
Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice
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DOI：
10.1016/j.pnpbp.2015.09.003
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发表时间：
2016-02-04
影响因子：
5.6
通讯作者：
Valverde, Olga
中科院分区：
文献类型：
--
作者：
Gracia-Rubio, Irene;Moscoso-Castro, Maria;Valverde, Olga
早期生活经历对大脑功能和行为起着关键作用。因此，儿童期的不良事件是成年期精神疾病（如情绪障碍）的风险因素。母亲分离是一种有效的母亲忽视小鼠模型，产生负面的早期生活经历，导致随后的情绪变化。情绪障碍已被发现与神经化学变化和神经递质缺陷有关，例如离散脑区中单胺的可用性降低。情绪变化如抑郁症通过吲哚胺2，3-双加氧酶对神经炎症因子的反应导致5-羟色胺可用性降低和犬尿氨酸代谢增强。这一机制涉及神经炎症因子对神经递质系统的调节，将情绪调节与神经免疫反应联系起来。在这种情况下，本研究的目的是调查母亲分离与早期断奶对小鼠情绪行为的影响。我们研究了神经炎症反应和状态的Dahan犬尿氨酸代谢途径在离散的大脑区域后，产妇分离。我们发现，生命早期的不良事件会增加青春期和成年期长期情绪变化的风险。这些情绪变化在女性中尤为严重。行为障碍与小胶质细胞激活和与情绪控制相关的大脑区域中的Dahan-kynurenine代谢紊乱有关。这一发现支持了神经炎症在情绪障碍中的突出作用。(C)2015 Elsevier Inc. All rights reserved.
Early life experiences play a key role in brain function and behaviour. Adverse events during childhood are therefore a risk factor for psychiatric disease during adulthood, such as mood disorders. Maternal separation is a validated mouse model for maternal neglect, producing negative early life experiences that result in subsequent emotional alteration. Mood disorders have been found to be associated with neurochemical changes and neurotransmitter deficits such as reduced availability of monoamines in discrete brain areas. Emotional alterations like depression result in reduced serotonin availability and enhanced kynurenine metabolism through the action of indoleamine 2, 3-dioxygenase in response to neuroinflammatory factors. This mechanism involves regulation of the neurotransmitter system by neuroinflammatory agents, linking mood regulation to neuroinmunological reactions. In this context, the aim of this study was to investigate the effects of maternal separation with early weaning on emotional behaviour in mice. We investigated neuroinflammatory responses and the state of the tryptophan-kynurenine metabolic pathway in discrete brain areas following maternal separation. We show that adverse events during early life increase risk of long-lasting emotional alterations during adolescence and adulthood. These emotional alterations are particularly severe in females. Behavioural impairments were associated with microglia activation and disturbed tryptophan-kynurenine metabolism in brain areas related to emotional control. This finding supports the preeminent role of neuroinflammation in emotional disorders. (C) 2015 Elsevier Inc. All rights reserved.