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破伤风毒素对大鼠海马细胞外氨基酸水平的影响:一项体内微透析研究。

Tetanus toxin-induced effects on extracellular amino acid levels in rat hippocampus: an in vivo microdialysis study.

作者信息

Britton P, Whitton P S, Fowler L J, Bowery N G

机构信息

Department of Pharmacology, School of Pharmacy, London, England.

出版信息

J Neurochem. 1996 Jul;67(1):324-9. doi: 10.1046/j.1471-4159.1996.67010324.x.

Abstract

Tetanus toxin is a potent neurotoxin that is widely considered to produce its effect through impairment of inhibitory neurotransmission. We report the effect of a single unilateral intrahippocampal injection of tetanus toxin on extracellular levels of neuroactive amino acids in freely moving rats, at times ranging between 1 and 7 days posttreatment. Tetanus toxin treatment did not alter extracellular levels of aspartate, glutamate, and taurine at any time during the study. However, although extracellular GABA levels were unaffected by toxin injection 1, 2, and 3 days after treatment, they were reduced (45 +/- 8% of contralateral vehicle-injected level) at day 7. Challenge with a high K+ concentration, 7 days after treatment, produced elevations in extracellular levels of taurine and GABA in both vehicle- and toxin-injected hippocampi, with evoked levels of GABA being lower in the toxin-treated side (39 +/- 16% of contralateral vehicle-injected level). Aspartate and glutamate levels were not increased by high-K+ infusion. These findings are discussed in relation to the possible role that an imbalance in excitatory/inhibitory tone may play in the production of tetanus toxin-induced neurodegeneration.

摘要

破伤风毒素是一种强效神经毒素,人们普遍认为它通过损害抑制性神经传递来产生作用。我们报告了在自由活动的大鼠中,单次单侧海马内注射破伤风毒素对治疗后1至7天神经活性氨基酸细胞外水平的影响。在研究期间的任何时候,破伤风毒素治疗均未改变天冬氨酸、谷氨酸和牛磺酸的细胞外水平。然而,尽管治疗后1、2和3天毒素注射未影响细胞外GABA水平,但在第7天其水平降低(对侧注射赋形剂水平的45±8%)。治疗7天后,用高钾浓度刺激,在注射赋形剂和毒素的海马中,牛磺酸和GABA的细胞外水平均升高,毒素处理侧诱发的GABA水平较低(对侧注射赋形剂水平的39±16%)。高钾灌注未增加天冬氨酸和谷氨酸水平。结合兴奋性/抑制性张力失衡在破伤风毒素诱导的神经退行性变产生中可能发挥的作用,对这些发现进行了讨论。

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