Developing brain as a target of toxicity.
Developing brain as a target of toxicity.
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DOI：
10.1289/ehp.95103s673
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发表时间：
1995-09
影响因子：
10.4
通讯作者：
Rodier PM
中科院分区：
文献类型：
--
作者：
Rodier PM
与其他器官相比，人类大脑的形成需要非常长的时间。虽然大部分基本结构在出生前就已经确定，但神经元的增殖和迁移在出生后仍在继续。血脑屏障直到生命第一年中期才完全发育。神经元之间的突触连接数量在两岁左右达到峰值，然后减少约一半。同样，受体和递质系统的发育以及髓磷脂的产生也有很大的出生后活动。许多已知会损害发育中的大脑的有毒物质会干扰这些发育过程中的一个或多个。那些具有抗有丝分裂作用的物质，如 X 射线和甲基汞，对结构有明显不同的影响，具体取决于暴露时形成的神经元。在产后早期，对干扰细胞产生的物质的脆弱性迅速降低。其他有毒物质，例如精神活性药物和改变激素水平的药物，在突触发生和递质系统的发育过程中尤其危险，因此在出生后数年内仍会产生损害。还有其他有毒物质，例如铅，似乎在大脑发育的后期阶段也能产生最大的影响，可能是通过干扰连接的修剪来实现的。旨在保护人类免受发育性神经毒性影响的指南需要考虑到大脑在经历不同发育阶段时敏感性的变化，以及有毒物质对成熟和发育中大脑影响的根本差异。
The human brain forms over an unusually long period compared to other organs. While most of the basic structure is laid down before birth, neuron proliferation and migration continue in the postnatal period. The blood-brain barrier is not fully developed until the middle of the first year of life. The number of synaptic connections between neurons reaches a peak around age two and is then trimmed back by about half. Similarly, there is great postnatal activity in the development of receptors and transmitter systems as well as in the production of myelin. Many of the toxic agents known to damage the developing brain interfere with one or more of these developmental processes. Those with antimitotic action, such as X-ray and methyl mercury, have distinctly different effects on structure depending on which neurons are forming at the time of exposure. Vulnerability to agents that interfere with cell production decreases rapidly over the early postnatal period. Other toxic substances, such as psychoactive drugs and agents that alter hormone levels, are especially hazardous during synaptogenesis and the development of transmitter systems, and thus continue to be damaging for years after birth. Still other toxic substances such as lead, seem to have their greatest effects during even later stages of brain development, perhaps by interfering with the trimming back of connections. Guidelines designed to protect human populations from developmental neurotoxicity need to take into account the changing sensitivity of the brain as it passes through different developmental stages, as well as the fundamental differences in the effects of toxicants on the mature and the developing brain.