Trans-urocanic acid facilitates spatial memory, implications for Alzheimer's disease

Xu-Dong Yu, Li Ao, Xiao-Ya Li , Yu Zhou, Xing Li, Zhiming He, Le Wang, James Reilly, Zhoujin Tan, Zhi-Yong Xiao*, Xinhua Shu*

*Corresponding author for this work

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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.
Original languageEnglish
Article number113827
Number of pages10
JournalPhysiology and Behavior
Early online date2 May 2022
Publication statusPublished - 1 Aug 2022


  • trans-urocanic acid
  • spatial memory
  • network pharmacology
  • alzheimer's disease

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience


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