Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder.
Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder.
复制标题
DOI：
10.1016/j.euroneuro.2017.09.003
复制
发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Walss-Bass C
中科院分区：
文献类型：
--
作者：
Fries GR;Colpo GD;Monroy-Jaramillo N;Zhao J;Zhao Z;Arnold JG;Bowden CL;Walss-Bass C
锂是治疗双相情感障碍(BD)最常用的处方药，但其有益作用的机制仍不清楚。我们的目的是比较锂在BD患者和对照组的淋巴母细胞系(LCLS)中的作用。LCL来自62名BD患者(根据DSM-IV)和17名年龄、性别和种族匹配的健康对照。患者从2012年2月至2014年10月从门诊招募。LCL细胞经1 mM锂离子处理7d后，进行基因芯片检测和实时定量聚合酶链式反应验证。分析了不同组之间的基线差异，以及每组内赋形剂和锂处理细胞之间的差异。通过途径富集法分析差异表达基因的生物学意义。两组之间的基线基因表达(调整后的p值和0.05)没有显著差异。对照LCLS的锂处理没有导致任何显著的差异。然而，锂改变了患者LCL中236个基因的表达；这些基因丰富了与细胞凋亡相关的信号通路。其中PIK3CG、SERP1和UPP1基因的表达变化通过实时定量聚合酶链式反应(Real-time PCR)得到验证。昼夜节律功能与CEBPG和FGF2的表达水平也存在显著的相关性。综上所述，我们的结果提示锂治疗诱导了BD LCLS中与凋亡途径相关的基因的表达变化。与对照组相比，锂在患者中的作用更明显，这表明这种药物具有疾病特异性作用。
Lithium is the most commonly prescribed medication for the treatment of bipolar disorder (BD), yet the mechanisms underlying its beneficial effects are still unclear. We aimed to compare the effects of lithium treatment in lymphoblastoid cell lines (LCLs) from BD patients and controls. LCLs were generated from sixty-two BD patients (based on DSM-IV) and seventeen healthy controls matched for age, sex, and ethnicity. Patients were recruited from outpatient clinics from February 2012 to October 2014. LCLs were treated with 1 mM lithium for 7 days followed by microarray gene expression assay and validation by real-time quantitative PCR. Baseline differences between groups, as well as differences between vehicle- and lithium-treated cells within each group were analyzed. The biological significance of differentially expressed genes was examined by pathway enrichment analysis. No significant differences in baseline gene expression (adjusted p-value < 0.05) were detected between groups. Lithium treatment of LCLs from controls did not lead to any significant differences. However, lithium altered the expression of 236 genes in LCLs from patients; those genes were enriched for signaling pathways related to apoptosis. Among those genes, the alterations in the expression of PIK3CG, SERP1 and UPP1 were validated by real-time PCR. A significant correlation was also found between circadian functioning and CEBPG and FGF2 expression levels. In summary, our results suggest that lithium treatment induces expression changes in genes associated with the apoptosis pathway in BD LCLs. The more pronounced effects of lithium in patients compared to controls suggest a disease-specific effect of this drug.
登录
查看更多内容
影响因子：
4.3
作者：
Dwivedi T;Zhang H
通讯作者：
Zhang H
影响因子：
3.7
作者：
Cruceanu, Cristiana;Alda, Martin;Turecki, Gustavo
通讯作者：
Turecki, Gustavo
影响因子：
5.4
作者：
Backlund, Lena;Nikamo, Pernilla;Osby, Urban
通讯作者：
Osby, Urban
影响因子：
4
作者：
Berghoefer, Anne;Alda, Martin;Pfennig, Andrea
通讯作者：
Pfennig, Andrea
影响因子：
6.7
作者：
Bowden, C. L.;Singh, V.;Chang, X.
通讯作者：
Chang, X.