School of Basic Medical Sciences, Shaoyang University, 422000, Shaoyang, China.
College of Chinese Medicine, Hunan University of Chinese Medicine, , 410208 Changsha, Hunan, China.
Physiol Behav. 2022 Aug 1;252:113827. doi: 10.1016/j.physbeh.2022.113827. Epub 2022 Apr 28.
Trans-urocanic acid (trans-UCA) is an isomer of cis-UCA and is widely distributed in the brain, predominantly in the hippocampus and prefrontal cortex. Previous studies have investigated the role of trans-UCA in non-spatial memory; however, its influence on spatial memory remains unclear. In the present study, network pharmacology strategy and behavioral testing were used to evaluate the role of trans-UCA in spatial memory and predict its possible mechanism. The results showed that there are 40 intersecting targets between trans-UCA and spatial memory identified by several databases and Venn diagram, indicating that trans-UCA may be involved in spatial memory. Behavioral results show that trans-UCA facilitates spatial working memory in the Y-maze test as well as spatial recognition memory acquisition, consolidation and retrieval in an object location recognition (OLR) task. Furthermore, PPI (protein-protein interaction) network analysis, GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses show that the molecular mechanisms underlying the enhancing effect of trans-UCA on spatial memory are mainly associated with the regulation of insulin, mitogen-activated protein kinase (MAPK) and nuclear factor Kappa B (NF-κB) signaling pathways, serotonergic synapse and arginine and proline metabolism. The results of this study suggest that trans-UCA facilitates spatial memory in the Y-maze test and OLR task and may offer therapeutic potential for Alzheimer's disease (AD). The underlying mechanisms predicted by network pharmacology should be further verified.
反式尿刊酸（trans-UCA）是顺式尿刊酸的异构体，广泛分布于大脑中，主要存在于海马体和前额叶皮层。先前的研究已经探讨了 trans-UCA 在非空间记忆中的作用，但它对空间记忆的影响尚不清楚。在本研究中，我们采用网络药理学策略和行为测试来评估 trans-UCA 在空间记忆中的作用，并预测其可能的机制。结果表明，通过几个数据库和韦恩图鉴定出 trans-UCA 与空间记忆之间存在 40 个交叉靶点，表明 trans-UCA 可能参与空间记忆。行为学结果表明，trans-UCA 可改善 Y 迷宫测试中的空间工作记忆以及物体位置识别（OLR）任务中的空间识别记忆获得、巩固和检索。此外，PPI（蛋白质-蛋白质相互作用）网络分析、GO（基因本体论）和 KEGG（京都基因与基因组百科全书）通路富集分析表明，trans-UCA 增强空间记忆的分子机制主要与胰岛素、丝裂原活化蛋白激酶（MAPK）和核因子 Kappa B（NF-κB）信号通路、5-羟色胺能突触以及精氨酸和脯氨酸代谢的调节有关。本研究结果表明，trans-UCA 可促进 Y 迷宫测试和 OLR 任务中的空间记忆，并可能为阿尔茨海默病（AD）提供治疗潜力。网络药理学预测的潜在机制需要进一步验证。
