Duvilanski B H, Selgas L, García-Bonacho M, Esquifino A I
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
J Neuroimmunol. 1998 Jul 1;87(1-2):189-96. doi: 10.1016/s0165-5728(98)00108-8.
Although the existence of central responses to inflammatory injuries was already reported, the existence of hypothalamic amino acid responses has been less explored. The present study was designed to characterize the 24-h changes in mediobasal hypothalamic excitatory and inhibitory amino acid neurotransmitter contents and to analyze the effect of Freund's complete adjuvant administration on these patterns. Also the effects of the immunosuppressant drug Cyclosporine was studied. The content of aspartate, glutamate, glutamine, GABA and taurine was measured by HPLC with fluorimetric detection. The results show the existence of specific daily rhythms of aspartate, glutamate, glutamine, GABA and taurine contents in the mediobasal hypothalamus of control rats. Maxima for these amino acids was found at midnight, although another peak of lesser magnitude, occurred during the light phase of the photoperiod, except for TAU in which both peaks were of similar magnitude. Freund's complete adjuvant administration did not modify the 24-h pattern of any amino acid studied. It reduced the midnight peak of glutamate, glutamine and GABA and increased that of taurine. Moreover, it increased and extended the midday peak of glutamate. Besides, Freund's adjuvant did not modify aspartate content at any time point studied. Cyclosporine pretreatment did not prevent the inhibitory effects of Freund's complete adjuvant on glutamate, glutamine and GABA midnight peaks. However, the drug blocked the increase in the content of taurine at midnight and increased its midday peak. Moreover, cyclosporine administration abolished the variations of ASP during the scotophase, as compared to control animals and shift delayed both peaks of glutamate. The results indicate the existence of a significant effect of immune-mediated inflammatory response of the mediobasal hypothalamic amino acids studied, at an early phase after Freund's adjuvant administration, and that these changes were partially sensitive to the immunosuppression induced by cyclosporine.
尽管已有报道称存在对炎症损伤的中枢反应，但对下丘脑氨基酸反应的研究较少。本研究旨在描述中基底下丘脑兴奋性和抑制性氨基酸神经递质含量的24小时变化，并分析弗氏完全佐剂给药对这些模式的影响。同时还研究了免疫抑制药物环孢素的作用。通过高效液相色谱-荧光检测法测定天冬氨酸、谷氨酸、谷氨酰胺、γ-氨基丁酸（GABA）和牛磺酸的含量。结果显示，对照大鼠中基底下丘脑的天冬氨酸、谷氨酸、谷氨酰胺、GABA和牛磺酸含量存在特定的每日节律。这些氨基酸的最大值出现在午夜，不过在光周期的光照阶段出现了另一个较小幅度的峰值，但牛磺酸的两个峰值幅度相似。弗氏完全佐剂给药并未改变所研究的任何氨基酸的24小时模式。它降低了谷氨酸、谷氨酰胺和GABA的午夜峰值，并增加了牛磺酸的午夜峰值。此外，它增加并延长了谷氨酸的中午峰值。此外，在任何研究的时间点，弗氏佐剂均未改变天冬氨酸含量。环孢素预处理并未阻止弗氏完全佐剂对谷氨酸、谷氨酰胺和GABA午夜峰值的抑制作用。然而，该药物阻断了午夜时牛磺酸含量的增加，并增加了其中午峰值。此外，与对照动物相比，环孢素给药消除了暗期天冬氨酸的变化，并使谷氨酸的两个峰值均出现延迟。结果表明，在弗氏佐剂给药后的早期阶段，免疫介导的炎症反应对所研究的中基底下丘脑氨基酸有显著影响，且这些变化对环孢素诱导的免疫抑制部分敏感。
