Martos Diána, Tuka Bernadett, Tanaka Masaru, Vécsei László, Telegdy Gyula
MTA-SZTE Neuroscience Research Group, Hungarian Academy of Sciences, University of Szeged (MTA-SZTE), Semmelweis u. 6, H-6725 Szeged, Hungary.
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Biomedicines. 2022 Apr 5;10(4):849. doi: 10.3390/biomedicines10040849.
Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases such as Alzheimer's and Parkinson's diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed for 24 h. High doses of KYNA (i.e., 20-40 μg/2 μL) significantly decreased the avoidance latency, whereas a low dose of KYNA (0.5 μg/2 μL) significantly elevated it compared with controls, suggesting that the low dose of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate systems in the nootropic effect. This study confirmed that a low dose of KYNA improved a memory component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.
犬尿喹啉酸（KYNA）是一种内源性色氨酸（Trp）代谢产物，已知具有神经保护特性。KYNA在痛觉、神经退行性变和神经炎症中起关键作用。在患有神经退行性疾病（如阿尔茨海默病和帕金森病）或精神疾病（如抑郁症和自闭症谱系障碍）的患者中观察到较低水平的KYNA，而较高水平的KYNA与精神分裂症的发病机制有关。关于神经保护的最佳浓度和神经毒性阈值知之甚少。在本研究中，通过小鼠被动回避试验研究了KYNA对记忆功能的影响。将六种不同剂量的KYNA脑室内注射给先前训练过的CFLP小鼠，并观察24小时。高剂量的KYNA（即20 - 40μg/2μL）显著缩短了回避潜伏期，而低剂量的KYNA（0.5μg/2μL）与对照组相比显著延长了回避潜伏期，表明低剂量的KYNA增强了记忆功能。此外，应用六种不同的受体阻滞剂来揭示KYNA诱导记忆增强的潜在机制。一系列测试揭示了5-羟色胺能、多巴胺能、α和β肾上腺素能以及阿片系统可能参与了益智作用。本研究证实，低剂量的KYNA改善了认知领域的记忆成分，这至少部分是由学习和记忆动物模型中的四种神经传递系统介导的。
