Neurotoxicologie Alimentaire et Bioactivité, MRCA/UR AFPA/INRA, Université de Lorraine, BP 4102, 57040 Metz, France.
Toxicology. 2012 Sep 4;299(1):44-54. doi: 10.1016/j.tox.2012.05.004. Epub 2012 May 15.
In this study, the neurobehavioral toxicity of lactational exposure to a representative mixture of the six indicator non-dioxin-like-polychlorinated biphenyls (∑6 NDL-PCBs 28, 52, 101, 138, 153 and 180) found in contaminated fish matrices were assessed in neonatal (postnatal day 0) to adult (postnatal day 275) mice. Thus, a battery of developmental, behavioral and cognitive tests was performed. The performance of mice whose mothers were orally exposed to ∑6 NDL-PCBs at environmental doses of 1 ng/kg, 10 ng/kg or 100 ng/kg was compared to that of mice whose mothers were orally exposed to vehicle. Our results showed that neonatal offspring mice exposed to ∑6 NDL-PCBs through lactation exhibited significantly longer turning reflexes on postnatal days 7 and 9 (p=0.001, p=0.002, respectively) at 100 ng/kg and showed a reduction in their general activity at 1 ng/kg (p=0.002) and 10 ng/kg (p=0.001) compared to controls. However, these developmental alterations were sex-dependent; only the female reflexes and male locomotor activity were affected. These disturbances were transient, and they disappeared with age. In addition, the males' visuomotor integration was also altered at the doses of 1 ng/kg (p=0.02) and 100 ng/kg (p=0.004), as revealed by the WESPOC test. Nevertheless, lactational exposure to ∑6 NDL-PCBs (1-100 ng/kg) resulted in persistent disturbances despite a long post-weaning period; the exposed mice exhibited anxious behavior that was detected at more progressive life stages, i.e., at postnatal days 40 and 160, using an elevated plus maze and the light/dark choice test, respectively. This persistent anxious behavior could be related to the overexpression of RyR₃ in the cerebellum via the disruption of calcium signaling in the neurons. We found no differences in the offspring mice with regard to their cognitive function and mood or mRNA neurotransmitter receptor gene expression in several brain areas, including 5-HT(1A), MOR₁ and GABA(Aα1), suggesting the absence of adverse effects of postnatal exposure to ∑6 NDL-PCBs under these conditions. Therefore, our results suggest that regular consumption of contaminated fish matrices by lactating women could be detrimental to the neurodevelopment of their newborns.
在这项研究中，评估了在受污染鱼基质中发现的六种代表性非二恶英类多氯联苯（∑6 NDL-PCBs28、52、101、138、153 和 180）的代表性混合物通过哺乳期暴露对新生（出生后第 0 天）至成年（出生后第 275 天）小鼠的神经行为毒性。因此，进行了一系列发育、行为和认知测试。将母亲经口暴露于 1ng/kg、10ng/kg 或 100ng/kg 环境剂量的∑6 NDL-PCBs 的小鼠的表现与经口暴露于载体的小鼠进行了比较。我们的结果表明，通过哺乳期暴露于∑6 NDL-PCBs 的新生后代小鼠在出生后第 7 天和第 9 天（p=0.001，p=0.002）的转身反射明显延长，在 100ng/kg 时表现出一般活动减少，而在 1ng/kg（p=0.002）和 10ng/kg（p=0.001）时与对照组相比，活动减少。然而，这些发育变化是性别依赖性的；只有雌性反射和雄性运动活动受到影响。这些干扰是短暂的，随着年龄的增长而消失。此外，雄性的视觉运动整合也在 1ng/kg（p=0.02）和 100ng/kg（p=0.004）的剂量下受到干扰，这一点在 WESPOC 测试中得到了揭示。然而，尽管断奶后有很长一段时间，但哺乳期暴露于∑6 NDL-PCBs（1-100ng/kg）仍会导致持续的干扰；暴露的小鼠在更成熟的生命阶段表现出焦虑行为，分别通过高架十字迷宫和明暗选择试验在出生后第 40 天和第 160 天检测到。这种持续的焦虑行为可能与通过神经元中钙信号的破坏导致小脑中 RyR₃的过度表达有关。我们没有发现后代小鼠在认知功能、情绪或几种大脑区域的 mRNA 神经递质受体基因表达方面存在差异，包括 5-HT(1A)、MOR₁ 和 GABA(Aα1)，这表明在这些条件下，新生儿期暴露于∑6 NDL-PCBs 不会产生不良影响。因此，我们的结果表明，哺乳期妇女经常食用受污染的鱼基质可能会损害新生儿的神经发育。
