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.

中文翻译：

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全球海洋生物污染物暴露的临床前模型：子宫内软骨藻酸暴露对新生儿行为和婴儿记忆的影响。


软骨藻酸 (DA) 是一种天然存在的海洋神经毒素，越来越被认为是一个重要的公共卫生问题。产前 DA 暴露是通过母亲食用受污染的贝类/有鳍鱼类而发生的。为了更好地了解与 DA 相关的胎儿风险，我们启动了一项纵向临床前研究，重点关注长期低剂量口服 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以及整个繁殖和怀孕期间每天口服0、0.075或0.15mg/kg/天的DA。这些剂量包括建议的 DA 人类每日耐受摄入量 (TDI)（0.075 毫克/公斤/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，对后代进行了新生儿评估，该评估以人类新生儿行为评估量表为模型，并使用新奇范式解决了一系列视觉识别记忆问题。结果表明，产前接触 DA 不会影响早期生存反射或对环境的反应能力。 1 至 2 个月大时进行的识别记忆评估结果表明，当测试问题相对容易解决时，暴露婴儿和对照婴儿表现出强劲的新颖性得分。延迟期的引入并没有降低性能。然而，当引入更困难的识别问题时，0.15 mg/kg DA 组的观看行为是随机的，婴儿未能对新的测试刺激表现出差异性视觉注意力。这一发现表明识别记忆存在微妙但显着的损害，并表明胎儿长期接触 DA 可能会影响认知过程的发育。