Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
Neurotoxicol Teratol. 2019 May-Jun;73:1-8. doi: 10.1016/j.ntt.2019.01.003. Epub 2019 Jan 25.
Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the recognition memory assessment, given between 1 and 2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential visual attention to novel test stimuli. This finding suggests subtle but significant impairment in recognition memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.
脱氧雪腐镰刀菌烯醇（Domoic acid，DA）是一种天然存在的海洋神经毒素，它日益被认为是一个重要的公共卫生问题。母体通过食用受污染的贝类/鱼类而摄入产前脱氧雪腐镰刀菌烯醇。为了更好地了解与 DA 相关的胎儿风险，我们开展了一项纵向的临床前研究，重点研究慢性低剂量口服 DA 暴露对生殖和发育的影响。为此，32 只成年雌性食蟹猴在繁殖前、繁殖期间和怀孕期间每天口服 0、0.075 或 0.15mg/kg/天的 DA。这些剂量包括提议的人类可耐受日摄入量（TDI）（0.075mg/kg/天）。成年雌性与未暴露的雄性交配。为了评估婴儿早期的发育情况，对后代进行了类似于人类新生儿行为评估量表的新生儿评估以及使用新颖性范式进行的一系列视觉识别记忆问题测试。结果表明，产前 DA 暴露不会影响早期生存反射或对环境的反应能力。在 1 至 2 个月大时进行的识别记忆评估结果表明，暴露组和对照组婴儿在测试问题相对容易解决时，表现出了很强的新颖性得分。引入延迟期并不会降低其表现。然而，当引入更困难的识别问题时，0.15mg/kg DA 组的观察行为是随机的，并且婴儿无法表现出对新颖测试刺激的不同视觉注意力。这一发现表明，识别记忆存在细微但显著的损伤，并表明慢性胎儿暴露于 DA 可能会影响正在发育的认知过程。
