Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development.
Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development.
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DOI：
10.2478/v10102-010-0042-y
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发表时间：
2008-12
影响因子：
--
通讯作者：
Mach M
中科院分区：
文献类型：
--
作者：
Dubovický M;Kovačovský P;Ujházy E;Navarová J;Brucknerová I;Mach M
发育中的生物体接触工业化学品和物理因素是发展神经行为障碍的一个严重风险因素，如注意力缺陷多动障碍、自闭症和智力迟钝。需要适当的动物模型来测试各种化学物质的发育神经毒性的潜在有害影响和机制。然而，在神经毒性研究中应考虑到人类与大鼠的大脑发育特征存在显著差异。传统的发育毒性和致畸性研究很难发现微妙的行为改变，在许多情况下，它们仍然是隐藏的。然而，它们可以通过使用特殊的行为，内分泌和/或药理学挑战来揭示，例如重复的行为测试，暴露于单一的压力刺激或药物。此外，目前的神经行为测试方案建议测试动物直到它们成年。然而，一些行为改变，如焦虑样行为或智力缺陷，可能会在发育后期变得明显。我们的实验和科学经验高度提示了测试潜在发育神经毒性的复杂方法。应特别强调对动物进行反复的行为测试，直至衰老，并使用适当的药理学和/或压力挑战。
Exposure of the developing organism to industrial chemicals and physical factors represents a serious risk factor for the development of neurobehavioral disorders, such as attention-deficit hyperactivity disorder, autism and mental retardation. Appropriate animal models are needed to test potentially harmful effects and mechanisms of developmental neurotoxicity of various chemical substances. However, there are significant human vs. rat differences in the brain developmental profile which should be taken into account in neurotoxicity studies. Subtle behavioral alterations are hard to detect by traditional developmental toxicity and teratogenicity studies, and in many cases they remain hidden. They can however be revealed by using special behavioral, endocrine and/or pharmacological challenges, such as repeated behavioral testing, exposure to single stressful stimulus or drugs. Further, current neurobehavioral test protocols recommend to test animals up to their adulthood. However some behavioral alterations, such as anxiety-like behavior or mental deficiency, may become manifest in later periods of development. Our experimental and scientific experiences are highly suggestive for a complex approach in testing potential developmental neurotoxicity. Strong emphasis should be given on repeated behavioral testing of animals up to senescence and on using proper pharmacological and/or stressful challenges.