THE TOXIC EFFECTS OF GLUTAMATE AND RELATED COMPOUNDS IN THE RETINA AND THE BRAIN
THE TOXIC EFFECTS OF GLUTAMATE AND RELATED COMPOUNDS IN THE RETINA AND THE BRAIN
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谷氨酸及相关化合物对视网膜和大脑的毒性作用
DOI：
10.1097/00006982-198200000-00020
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
J. Olney
中科院分区：
文献类型：
--
作者：
J. Olney
本文综述了一类有趣的氨基酸——谷氨酸、天冬氨酸及其某些结构类似物的相关信息，其中一些是神经递质候选者，所有这些都具有神经兴奋性和神经毒性活性。兴奋性毒性概念的证据，认为兴奋性和可能突触相关的机制是这些化合物的神经毒性的基础。与许多主要在轴突引起毒性变化的环境神经毒物不同，这些毒剂攻击神经元的树突部分，这导致它们被用作“保留轴突”的损伤剂。无论是系统给药还是直接显微注射到中枢神经系统，它们都能从浸润区域删除固有神经元，而不会干扰穿过或终止于浸润区域的轴突。因此，它们是研究中枢神经系统解剖通路和结构-功能关系的潜在有用工具。它们被用作系统研究工具的基础——它们可以从血液进入视网膜和大脑的特定区域，即心室周围器官——也是考虑将它们用作食品添加剂或药物有潜在危险的基础。考虑了消费者可能接触这些物质的方式，并讨论了相关的风险机制。
This paper has reviewed information pertaining to an interesting group of amino acids--glutamate, aspartate, and certain of their structural analogs, some of which are neurotransmitter candidates, and all of which have both neuroexcitatory and neurotoxic activities. Evidence for the excitotoxic concept, which holds that an excitatory and possibly synapse-related mechanism underlies the neurotoxicity of these compounds, is presented. Unlike a number of environmental neurotoxicants which induce toxic changes primarily in axons, these agents attack the dendrosomal portions of the neuron, which has led to their use as "axon-sparing" lesioning agents. When administered either systemically or by direct microinjection into the CNS, they delete intrinsic neurons from infiltrated regions without disturbing axons that are passing through or terminating therein. They are potentially useful tools, therefore, for studying anatomical pathways and structure-function relations in the CNS. The basis for their use as systemic investigational tools--that they have access from blood to the retina and specialized regions of brain, the circumventricular organs--is also the basis for considering them potentially hazardous for use as food additives or drugs. Ways in which the consumer may be exposed to these agents are considered and relevant mechanisms of risk are discussed.