DEVELOPING BRAIN AS A TARGET OF TOXICITY
DEVELOPING BRAIN AS A TARGET OF TOXICITY
复制标题
DOI：
10.2307/3432351
复制
发表时间：
1995-09-01
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，人类大脑的形成时间异常长。而大部分的基本结构是在出生前就确定下来的。神经元增殖和迁移在出生后时期继续。血脑屏障直到一岁中期才完全发育。神经元之间的突触连接数量在两岁左右达到高峰，然后减少一半左右。同样，在受体和递质系统的发育以及髓磷脂的产生方面，出生后也有很大的活动。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。具有抗有丝分裂作用的药物，如X射线和甲基汞。对结构有明显不同的影响，这取决于暴露时形成的神经元。在出生后早期，对干扰细胞生成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剂，在突触发生和递质系统的发育过程中特别危险，因此在出生后的数年内继续具有损害性。还有一些有毒物质，如铅，似乎在大脑发育的后期阶段影响最大，可能是通过干扰连接的修剪。旨在保护人类群体免受发育神经毒性影响的准则需要考虑到大脑在经历不同发育阶段时不断变化的敏感性。以及毒物对成熟和发育中的大脑的影响的根本差异。
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 expecially 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.