Urinary volatilome analysis in a mouse model of anxiety and depression
Urinary volatilome analysis in a mouse model of anxiety and depression
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DOI：
10.1371/journal.pone.0229269
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发表时间：
2020-02-21
期刊：
影响因子：
3.7
通讯作者：
Kato, Keiko
中科院分区：
文献类型：
--
作者：
Fujita, Akiko;Okuno, Takaya;Kato, Keiko
精神障碍包括抑郁症和焦虑症，包括具有不同症状的广泛病症。我们已经在St 3gal 4基因缺陷的小鼠中开发了抑郁/焦虑的小鼠模型。在这项研究中，我们进行了比较分析尿挥发性有机化合物（VOCs）在St 3gal 4缺陷（St 3gal 4-KO）和野生型小鼠使用气相色谱-质谱，我们筛选出18个推定的VOCs。主成分分析（PCA）的基础上，这些挥发性有机化合物确定了一个主要的组11挥发性有机化合物，其中两组澄清的层次聚类分析。一组包括6种VOC（戊酸，4-甲基-，乙酯; 3-庚酮，6-甲基;苯甲醛; 5，9-十一碳二烯-2-醇，6，10-二甲基;和未知化合物RI 1291和RI 1237）与惊吓反应（r = 0.620）相关，这与无意识的防御反应有关。另一组包括两种VOC（β-法呢烯和α-法呢烯），其包含在KO小鼠中增加的信息素。接下来，雄性小鼠与处于发情期的雌性小鼠进行社会行为测试，显示KO雄性小鼠对雌性小鼠的接近减少。对接触前后尿中挥发性有机物的比较分析表明，接触前后尿中的6种挥发性有机物没有发生变化。然而，在WT小鼠中，两种法呢烯在遭遇后增加，达到在KO小鼠中观察到的水平，这在遭遇后没有改变。综上所述，这些结果表明St 3gal 4参与调节尿VOC。此外，通过比较St 3gal 4-KO小鼠与WT小鼠发现的VOC簇与不同的情绪行为相关。
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.