Ibotenic acid-induced neuronal degeneration: A morphological and neurochemical study
Ibotenic acid-induced neuronal degeneration: A morphological and neurochemical study
复制标题
鹅膏蕈酸诱导的神经元变性：形态学和神经化学研究
DOI：
--
复制
发表时间：
1979
影响因子：
2
通讯作者：
L. Terenius
中科院分区：
文献类型：
--
作者：
R. Schwarcz;T. Hökfelt;K. Fuxe;G. Jonsson;M. Goldstein;L. Terenius
脑内注射谷氨酸的构象限制性类似物伊博tenic酸，已经在大鼠脑内评估了可能的神经毒性作用，并与kainic酸进行了比较。光镜分析显示，伊博tenic酸在研究的所有区域，即纹状体、海马体、黑质和梨状皮质，产生了明显的神经细胞消失。远离注射部位的病变未见。通路轴突和外源性神经末梢似乎没有受损，例如，除了导管周围的一小块区域外，新纹状体的多巴胺能末梢未见明显退化。在新纹状体中，脑啡肽免疫反应的神经元细胞体和神经末梢在注射伊博滕酸后消失。在黑质注射酪氨酸羟化酶后，紧带内免疫反应的细胞体消失，而对脑啡肽免疫反应的神经纤维未见一定影响。纹状体突触体和膜制备的体外实验表明，伊伯tenic酸与kainic酸的不同之处在于，它对高亲和力谷氨酸摄取没有明显的抑制作用，对3H-kainic酸结合位点的亲和力较低。此外，伊博滕酸不会干扰其他递质受体的一些放射性配体的结合。与kainic酸相比，ibotenic酸的优点是对动物的毒性更小，并且产生更离散的病变，这可能是由于更快的代谢和/或其他基本的生化差异。由于这些特殊的特征，伊博滕酸似乎代表了一种有价值的新工具，用于中枢神经系统的形态和功能分析。
SummaryPossible neurotoxic actions of intracerebral injections of ibotenic acid, a conformationally restricted analogue of glutamic acid, have been evaluated in rat brain and compared with those of kainic acid.Light microscopical analysis revealed that ibotenic acid produced a marked disappearance of nerve cells in all areas studied, namely striatum, the hippocampal formation, substantia nigra and piriform cortex. Lesions in areas distant to the injection site were not seen. Axons of passage and nerve terminals of extrinsic origin did not seem to be damaged, since, e.g., no apparent degeneration of the dopaminergic terminals in the neostriatum was observed except for a small area surrounding the cannula. In the neostriatum, enkephalin immunoreactive neuronal cell bodies as well as nerve terminals disappeared after injection of ibotenic acid into this nucleus. After injection into the substantia nigra tyrosine hydroxylase immunoreactive cell bodies in the zona compacta disappeared, whereas no certain effect could be seen on the enkephalin immunoreactive nerve fibers.In vitro experiments, conducted with striatal synaptosomal and membrane preparations, showed that ibotenic acid differed from kainic acid by being devoid of a significant inhibitory effect on high affinity glutamate uptake and by having a low affinity for 3H-kainic acid binding sites. Furthermore, ibotenic acid did not interfere with the binding of a number of radioligands for other transmitter receptors.As compared to kainic acid, ibotenic acid has the advantage of being less toxic to the animals and of producing more discrete lesions, possibly due to faster metabolism and/or other fundamental biochemical differences. Because of these special features, ibotenic acid seems to represent a valuable new tool in the morphological and functional analysis of central neuronal systems.