Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.
Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.
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DOI：
10.1016/j.bbr.2016.03.039
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发表时间：
2016-07-15
影响因子：
2.7
通讯作者：
Lahvis GP
中科院分区：
文献类型：
--
作者：
Mills BD;Pearce HL;Khan O;Jarrett BR;Fair DA;Lahvis GP
软骨藻酸（DA）是一种由海藻产生的毒素，主要因其在遗忘贝类中毒的孤立爆发中的作用以及对海洋哺乳动物，特别是加州海狮造成的损害而闻名。DA的致死作用通常在癫痫发作和昏迷之前发生。在发育过程中暴露于DA会对大脑发育产生微妙和高度持久的影响，包括类似精神分裂症诊断特征的行为变化和我们认为与自闭症谱系障碍（ASD）相关的社会行为异常。为了更全面地检验这一假设，我们选择检查子宫内暴露于DA的青春期小鼠与ASD相关的终点，特别是社会行为和网络结构的变化，后者通过静息状态功能连接（rsfcMRI）测量。我们发现，在子宫内暴露于DA的男性后代表达的社会互动和非典型模式的功能连接的前扣带，默认模式网络的区域，是社会功能的关键的再现下降。我们还发现，在涉及奖励、社会和感官体验的处理区域，全球拓扑结构出现了中断。最后，我们发现，DA暴露的男性表达了局部过度连接的模式。大脑连接的这些异常与ASD的连接模式相似，并有助于验证DA暴露小鼠作为这种精神残疾的模型。
Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rsfcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability.