Indispensable amino acid deficiency and increased seizure susceptibility in rats
Indispensable amino acid deficiency and increased seizure susceptibility in rats
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DOI：
10.1152/ajpregu.1996.271.1.r18
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发表时间：
1996-07-01
影响因子：
2.8
通讯作者：
Washburn, DS
中科院分区：
文献类型：
--
作者：
Gietzen, DW;Dixon, KD;Washburn, DS
反复阈下刺激边缘脑区增加癫痫实验模型的发作易感性。此外，急性饮食中必需氨基酸（IAA）缺乏会激活前梨状皮质（APC），这是大鼠易发作的边缘脑区域。基于这两项发现，我们假设长期暴露于缺乏iaa的饮食中激活APC可能会增加癫痫易感性。几种非必需氨基酸神经递质在癫痫发作中很重要，但在癫痫发作模型中缺乏非递质IAAs尚未得到很好的研究。在四项试验中，我们在组氨酸、异亮氨酸或苏氨酸缺乏的大鼠和对照组的APC中腹腔注射戊四唑或双库兰。缺乏症患者癫痫易感性增加；动物观察到癫痫发作的严重程度增加，化学兴奋剂剂量和癫痫发作时间的阈值降低，或两者的组合。配对喂养的对照组表明，这种影响不是由于能量不足。这一新颖而有力的发现表明，IAA缺乏可能会通过APC的反复激活而增加癫痫发作的易感性。
Repeated subthreshold stimulation of limbic brain areas increases seizure susceptibility in experimental models of epilepsy. In addition, acute dietary indispensable amino acid (IAA) deficiency activates the anterior piriform cortex (APC), a seizure-prone limbic brain area in the rat. Based on these two findings, we hypothesized that activation of the APC by chronic exposure to IAA-deficient diets might increase seizure susceptibility. Several nonessential amino acid neurotransmitters are important in seizures, but deficiencies of nontransmitter IAAs have not been well studied in seizure models. In four trials, we made injections of pentylenetetrazole intraperitoneally or of bicuculline into the APC in histidine-, isoleucine-, or threonine-deficient rats and controls. Increased susceptibility to seizures in the deficient; animals was observed as increased severity of the seizures, decreased threshold for the dose of the chemostimulant and time to seizure, or a combination thereof. Pair-fed controls showed that this effect was not due to an energy deficit. This novel but-robust finding suggests that IAA deficiency may increase vulnerability to seizures by repeated activation of the APC.