Urinary volatilome analysis in a mouse model of anxiety and depression

Psychiatric disorders including depression and anxiety comprise a broad range of conditions with different symptoms. We have developed a mouse model of depression/anxiety in mice deficient in the St3gal4 gene. In this study, we performed a comparative analysis of urinary volatile organic compounds (VOCs) in St3gal4-deficient (St3gal4-KO) and wild-type mice using gas chromatography-mass spectrometry, and we screened 18 putative VOCs. Principal component analysis (PCA) based on these VOCs identified a major group of 11 VOCs, from which two groups were clarified by hierarchical clustering analysis. One group including six VOCs (pentanoic acid, 4-methyl-, ethyl ester; 3-heptanone, 6-methyl; benzaldehyde; 5,9-undecadien-2-ol, 6,10-dimethyl; and unknown compounds RI1291 and RI1237) was correlated with the startle response (r = 0.620), which is related to an unconscious defensive response. The other group including two VOCs (beta-farnesene and alpha-farnesene) comprised pheromones which increased in KO mice. Next, male mice underwent a social behavior test with female mice in the estrus stage, showing reduced access of KO male mice to female mice. Comparative analysis of urinary VOCs before and after encounters revealed that the six VOCs were not changed by these encounters. However, in WT mice, the two farnesenes increased after the encounters, reaching the level observed in KO mice, which was not altered following the encounter. Taken together, these results indicated that St3gal4 was involved in modulating urinary VOCs. Moreover, VOC clusters discovered by comparison of St3gal4-KO mice with WT mice were correlated with differential emotional behaviors.