Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
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DOI：
10.1016/j.bbrep.2019.100660
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发表时间：
2019-09-01
影响因子：
2.7
通讯作者：
Sakane, Fumio
中科院分区：
文献类型：
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作者：
Komenoi, Suguru;Suzuki, Yuji;Sakane, Fumio
我们发现二酰基甘油激酶eta （DGKn）敲除（KO）小鼠表现出双相情感障碍（BPD）药物敏感的躁狂样行为。然而，引起躁狂样异常行为的分子机制尚不清楚。在本研究中，采用微阵列分析来确定DGK eta-KO小鼠大脑中基因表达的全局变化。我们发现DGK eta-KO脑有43个差异表达基因，并有以下5条受影响的生物学途径：“神经活性配体-受体相互作用”、“RNA聚合酶II转录”、“胞质钙离子浓度”、“Jak-STAT信号通路”和“ERK1/2级联”。有趣的是，泌乳素和生长激素的mRNA水平在BPD患者和模型动物中增加得最多。值得注意的是，这五种生物通路中至少有一个基因在泌乳素、生长激素、叉头盒P3、胰高血糖素样肽1受体和白细胞介素1 β中，这些基因先前与BPD有关。与微阵列数据一致，DGK eta-KO脑中磷酸化的ERK1/2水平降低。微阵列分析显示，几个甘油脂代谢相关基因的表达水平也发生了变化。液相色谱-质谱分析显示，DGK - eta缺乏导致几种含多不饱和脂肪酸（PUFA）的磷脂酸（PA）分子种显著减少，表明这种减少影响了PUFA的代谢。有趣的是，DGK eta-KO小鼠血液中含有pufa的溶血opa种类明显减少。综上所述，我们的研究不仅为获得对躁狂样行为潜在机制的新见解提供了关键的广泛知识，而且为开发BPD诊断提供了信息。
We have revealed that diacylglycerol kinase eta (DGKn)-knockout (KO) mice display bipolar disorder (BPD) remedy-sensitive mania-like behaviors. However, the molecular mechanisms causing the mania-like abnormal behaviors remain unclear. In the present study, microarray analysis was performed to determine global changes in gene expression in the DGK eta-KO mouse brain. We found that the DGK eta-KO brain had 43 differentially expressed genes and the following five affected biological pathways: "neuroactive ligand-receptor interaction", "transcription by RNA polymerase II", "cytosolic calcium ion concentration", "Jak-STAT signaling pathway" and "ERK1/2 cascade". Interestingly, mRNA levels of prolactin and growth hormone, which are augmented in BPD patients and model animals, were most strongly increased. Notably, all five biological pathways include at least one gene among prolactin, growth hormone, forkhead box P3, glucagon-like peptide 1 receptor and interleukin 1 beta, which were previously implicated in BPD. Consistent with the microarray data, phosphorylated ERK1/2 levels were decreased in the DGK eta-KO brain. Microarray analysis showed that the expression levels of several glycerolipid metabolism-related genes were also changed. Liquid chromatography-mass spectrometry revealed that several polyunsaturated fatty acid (PUFA)-containing phosphatidic acid (PA) molecular species were significantly decreased as a result of DGK eta deficiency, suggesting that the decrease affects PUFA metabolism. Intriguingly, the PUFA-containing lysoPA species were markedly decreased in DGK eta-KO mouse blood. Taken together, our study provides not only key broad knowledge to gain novel insights into the underlying mechanisms for the mania-like behaviors but also information for developing BPD diagnostics.