Cline H T, Witte S, Jones K W
Cold Spring Harbor Laboratory, NY 11724, USA.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9915-20. doi: 10.1073/pnas.93.18.9915.
The developing brain is particularly susceptible to lead toxicity; however, the cellular effects of lead on neuronal development are not well understood. The effect of exposure to nanomolar concentrations of lead on several parameters of the developing retinotectal system of frog tadpoles was tested. Lead severely reduced the area and branchtip number of retinal ganglion cell axon arborizations within the optic tectum at submicromolar concentrations. These effects of lead on neuronal growth are more dramatic and occur at lower exposure levels than previously reported. Lead exposure did not interfere with the development of retinotectal topography. The deficient neuronal growth does not appear to be secondary to impaired synaptic transmission, because concentrations of lead that stunted neuronal growth were lower than those required to block synaptic transmission. Subsequent treatment of lead-exposed animals with the chelating agent 2,3-dimercaptosuccinic acid completely reversed the effect of lead on neuronal growth. These studies indicate that impaired neuronal growth may be responsible in part for lead-induced cognitive deficits and that chelator treatment counteracts this effect.
发育中的大脑对铅毒性尤为敏感；然而，铅对神经元发育的细胞效应尚未得到充分了解。测试了暴露于纳摩尔浓度的铅对青蛙蝌蚪发育中的视网膜顶盖系统的几个参数的影响。在亚微摩尔浓度下，铅严重减少了视顶盖内视网膜神经节细胞轴突分支的面积和分支尖端数量。铅对神经元生长的这些影响比以前报道的更为显著，且在较低暴露水平下就会出现。铅暴露并未干扰视网膜顶盖拓扑结构的发育。神经元生长不足似乎并非继发于突触传递受损，因为阻碍神经元生长的铅浓度低于阻断突触传递所需的浓度。随后用螯合剂2,3 - 二巯基丁二酸对铅暴露动物进行治疗，完全逆转了铅对神经元生长的影响。这些研究表明，神经元生长受损可能部分导致了铅诱导的认知缺陷，而螯合剂治疗可抵消这种影响。
