Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity
Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity
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DOI：
10.1016/j.cell.2014.12.028
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发表时间：
2015-01-15
期刊：
影响因子：
64.5
通讯作者：
Ashrafi, Kaveh
中科院分区：
文献类型：
--
作者：
Lemieux, George A.;Cunningham, Katherine A.;Ashrafi, Kaveh
色氨酸代谢的犬尿氨酸途径参与了多种脑疾病的发病机制，但其生理功能尚不清楚。我们报道，犬尿烯酸，在这一途径中的代谢产物，作为一种调节剂的食物依赖的行为可塑性在C。优美的在C.当进食后遇到食物时，秀丽线虫会改变各种行为，包括进食速度。神经产生的犬尿烯酸水平通过禁食耗尽，导致表达NMDA受体的中间神经元的激活和神经肽-y样信号传导轴的启动，当动物再次遇到食物时，神经肽-y样信号传导轴通过增强的5-羟色胺释放来促进进食量的增加。在再喂养时，犬尿烯酸水平最终得到补充，结束了高喂养期。由于色氨酸是一种必需氨基酸，这些发现表明犬尿烯酸的生理作用是直接将代谢与NMDA和多巴胺能回路的活性联系起来，这些回路调节广泛的行为和生理。
The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases, but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food-dependent behavioral plasticity in C. elegans. The experience of fasting in C. elegans alters a variety of behaviors, including feeding rate, when food is encountered postfast. Levels of neurally produced kynurenic acid are depleted by fasting, leading to activation of NMDA-receptor-expressing interneurons and initiation of a neuropeptide-y-like signaling axis that promotes elevated feeding through enhanced serotonin release when animals re-encounter food. Upon refeeding, kynurenic acid levels are eventually replenished, ending the elevated feeding period. Because tryptophan is an essential amino acid, these findings suggest that a physiological role of kynurenic acid is in directly linking metabolism to activity of NMDA and serotonergic circuits, which regulate a broad range of behaviors and physiologies.