Effects of in vivo sodium azide administration on the immunohistochemical localization of kynurenine aminotransferase in the rat brain.
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| Abstract |
Endogenous excitotoxins that act on receptors of cerebral excitatory amino acids play important roles in the pathogenesis of excitotoxic brain diseases. Activation of excitatory amino acid receptors results in neuronal death characteristic of these disorders. Kynurenic acid, a powerful endogenous excitatory amino acid receptor antagonist, which is therefore widely regarded as a potent neuroprotective agent, is produced from its biological precursor, L-kynurenine, by the action of the enzyme kynurenine aminotransferase-I. The chemical hypoxia induced by mitochondrial toxins produces a secondary excitotoxicity, leading to the activation of N-methyl-D-aspartate receptors. Accordingly, sodium azide, an inhibitor of cytochrome oxidase, induces the release of excitotoxins via an energy impairment and this, in turn, results in neurodegeneration. Since energy-dependent secondary excitotoxic mechanisms also account for the pathogenesis of neurodegenerative diseases, a study was made of the effects of sodium azide on the immunohistochemical localization of kynurenine aminotransferase-I. After in vivo administration of sodium azide for five days, a markedly decreased glial kynurenine aminotransferase-I immunoreactivity was found by immunohistochemical techniques in the glial cells of the striatum, hippocampus, dentate gyrus and temporal cortex; at the same time, kynurenine aminotransferase-I started to be expressed by nerve cells which had not been immunoreactive previously. The accumulation of kynurenine aminotransferase-I reaction product around the ribosomes of neuronal endoplasmic reticulum suggests de novo synthesis of kynurenine aminotransferase-I in the reactive nerve cells.
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| Authors | E Knyihár-Csillik, E Okuno, L Vécsei |
| Journal | Neuroscience (Neuroscience) Vol. 94 Issue 1 Pg. 269-77 ( 1999) ISSN: 0306-4522 [Print] United States |
| PMID | 10613517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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