Jones Karen L, Smith Ryan M, Edwards Kristin S, Givens Bennet, Tilley Michael R, Beversdorf David Q
Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO 65211, USA.
Int J Dev Neurosci. 2010 Oct;28(6):529-36. doi: 10.1016/j.ijdevneu.2010.05.002. Epub 2010 May 12.
Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring.
多项研究表明，产前应激可能是自闭症谱系障碍发展的一个风险因素。然而，许多在产前暴露于应激的儿童出生时健康且发育正常，这表明其他因素必定也与自闭症有关。因此，对应激反应性有影响的基因可能会加剧成年后代中由产前应激介导的行为变化。一个与应激反应性增加相关的候选基因编码血清素转运体。具体而言，血清素转运体基因上游的一个插入/缺失（长/短等位基因）多态性与血清素转运体的差异表达和功能以及对应激源的增强反应相关。杂合血清素转运体基因敲除小鼠的血清素转运体表达降低，类似于人类的短多态性。在本研究中，评估了产前应激和母本血清素转运体基因型在小鼠中的作用，以确定它们的联合作用是否会导致成年后代的社交行为减少。将怀孕的血清素转运体杂合基因敲除母鼠和野生型母鼠置于对照条件下或使其遭受慢性可变应激。随后使用三室社交接近任务、超声波发声检测、高架十字迷宫和旷场任务对成年后代的社交互动和焦虑进行评估。结果表明，产前应激和母本血清素转运体表达降低可能共同作用，使后代的社交互动和社交兴趣发生变化，这与自闭症谱系障碍中观察到的情况一致。该数据表明母本血清素转运体基因型和产前应激可能共同作用，导致后代出现类似自闭症的行为。
