我们已经发现,二酰甘油激酶η(DGKη)敲除(KO)小鼠表现出双相情感障碍(BPD)补救敏感的躁狂症样行为。然而,引起躁狂症样异常行为的分子机制尚不清楚。在本研究中,进行微阵列分析以确定DGKη-KO小鼠脑中基因表达的整体变化。我们发现DGKη-KO大脑有43个差异表达基因和以下五个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”,“细胞溶质钙离子浓度”,“Jak-STAT信号通路”和“ERK1/2级联”。有趣的是,催乳素和生长激素的mRNA水平,在BPD患者和模型动物中增加,增长最为强劲。值得注意的是,所有五个生物学途径包括催乳素中的至少一个基因,生长激素,叉头盒P3,胰高血糖素样肽1受体和白细胞介素1β,以前与BPD有关。与微阵列数据一致,DGKη-KO脑中磷酸化ERK1/2水平降低。基因芯片分析表明,几种与甘油脂代谢相关的基因的表达水平也发生了变化。液相色谱-质谱显示,由于DGKη缺乏,几种含有多不饱和脂肪酸(PUFA)的磷脂酸(PA)分子物种显着减少,表明减少影响PUFA代谢。有趣的是,DGKη-KO小鼠血液中含有PUFA的lysoPA物种显着减少。一起来看,我们的研究不仅为了解躁狂样行为的潜在机制提供了重要的广泛知识,而且为开发BPD诊断提供了信息.
We have revealed that diacylglycerol kinase η (DGKη)-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 DGKη-KO mouse brain. We found that the DGKη-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 1β, which were previously implicated in BPD. Consistent with the microarray data, phosphorylated ERK1/2 levels were decreased in the DGKη-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 DGKη deficiency, suggesting that the decrease affects PUFA metabolism. Intriguingly, the PUFA-containing lysoPA species were markedly decreased in DGKη-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.