Department of Biological Sciences, NC State University, Raleigh, NC 27695, USA.
Nicholas School of the Environment, Levine Science Research Center, Duke University, Durham, NC 27710, USA.
Neurotoxicol Teratol. 2020 May-Jun;79:106840. doi: 10.1016/j.ntt.2019.106840. Epub 2019 Nov 12.
The rapidly rising incidence of neurodevelopmental disorders with social deficits is raising concern that developmental exposure to environmental contaminants may be contributory. Firemaster 550 (FM 550) is one of the most prevalent flame-retardant (FR) mixtures used in foam-based furniture and baby products and contains both brominated and organophosphate components. We and others have published evidence of developmental neurotoxicity and sex specific effects of FM 550 on anxiety-like and exploratory behaviors. Using a prosocial animal model, we investigated the impact of perinatal FM 550 exposure on a range of socioemotional behaviors including anxiety, attachment, and memory. Virtually unknown to toxicologists, but widely used in the behavioral neurosciences, the prairie vole (Microtus ochrogaster) is a uniquely valuable model organism for examining environmental factors on sociality because this species is spontaneously prosocial, biparental, and displays attachment behaviors including pair bonding. Dams were exposed to 0, 500, 1000, or 2000 μg of FM 550 via subcutaneous (sc) injections throughout gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring of both sexes were then subjected to multiple tasks including open field, novel object recognition, and partner preference. Effects were dose responsive and sex-specific, with females more greatly affected. Exposure-related outcomes in females included elevated anxiety, decreased social interaction, decreased exploratory motivation, and aversion to novelty. Exposed males also had social deficits, with males in all three dose groups failing to show a partner preference. Our studies demonstrate the utility of the prairie vole for investigating the impact of chemical exposures on social behavior and support the hypothesis that developmental FR exposure impacts the social brain. Future studies will probe the possible mechanisms by which these effects arise.
神经发育障碍的发病率迅速上升，这些障碍伴有社交缺陷，这让人担忧环境污染物的发育暴露可能是致病因素之一。Firemaster 550（FM 550）是用于泡沫家具和婴儿产品的最常见阻燃剂（FR）混合物之一，它含有溴化和有机磷成分。我们和其他人已经发表了证据表明，FM 550 对焦虑样和探索行为具有发育神经毒性和性别特异性影响。使用亲社会动物模型，我们研究了围产期 FM 550 暴露对一系列社会情感行为的影响，包括焦虑、依恋和记忆。草原田鼠（Microtus ochrogaster）对毒理学家来说几乎是未知的，但在行为神经科学中广泛使用，它是一种非常有价值的模型生物，可用于研究环境因素对社会性的影响，因为这种物种天生是亲社会的、双亲的，并表现出依恋行为，包括配对结合。在整个妊娠期，通过皮下（sc）注射，母鼠暴露于 0、500、1000 或 2000μg 的 FM 550，从出生后的第一天开始，幼崽直接暴露，直到断奶。然后，雌雄成年后代接受多项任务，包括旷场、新物体识别和配偶偏好。影响与剂量呈正相关，且具有性别特异性，雌性受影响更大。雌性暴露相关的结果包括焦虑增加、社交互动减少、探索动机减少以及对新奇事物的厌恶。暴露的雄性也有社交缺陷，所有三个剂量组的雄性都没有表现出对配偶的偏好。我们的研究表明，草原田鼠可用于研究化学暴露对社会行为的影响，并支持发育 FR 暴露影响社交大脑的假说。未来的研究将探讨这些影响产生的可能机制。
