Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder.
Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder.
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DOI：
10.1002/ajmg.b.32257
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发表时间：
2014-09
影响因子：
2.8
通讯作者：
Cohen, Bruce M.
中科院分区：
文献类型：
--
作者：
Zubenko, George S.;Hughes, Hugh B.;Jordan, Rick M.;Lyons-Weiler, James;Cohen, Bruce M.
我们最近报道了一种基于病因学的重组小鼠模型的创建和初步表征，该模型是一种严重的遗传性重度抑郁症（MDD）。这是通过用来自人类CREB 1启动子的6个碱基的DNA序列替换相应的小鼠DNA序列来实现的，人类CREB 1启动子与来自复发性早发性MDD（RE-MDD）家族的个体的MDD相关。在目前的研究中，我们探讨了致病性Creb 1等位基因对小鼠海马基因表达的影响，这是一个在MDD中结构和功能改变的脑区。使用Illumina MouseWG-6 v2.0 Expression BeadChip微阵列进行小鼠全基因组分析。单变量分析确定了269个差异表达基因的突变小鼠海马。通路分析突出了11个KEGG通路：磷脂酰肌醇信号系统，其已广泛涉及MDD、双相情感障碍和情绪稳定剂的作用;间隙连接和长时程增强，其介导MDD中经常受损的认知和记忆功能;心肌收缩、胰岛素信号通路和三种神经退行性脑部疾病（阿尔茨海默氏病、帕金森氏病和亨廷顿氏病）;影响蛋白质合成/降解的核糖体和蛋白酶体途径;以及对能量产生至关重要的氧化磷酸化途径。这些发现说明了这种同源C57 BL/6重组小鼠作为RE-MDD模型的优点，并证明了其突出有助于MDD生物学的分子和细胞途径的潜力。这些结果也为我们理解MDD与其他疾病合并症的机制提供了信息。
We have recently reported the creation and initial characterization of an etiology-based recombinant mouse model of a severe and inherited form of Major Depressive Disorder (MDD). This was achieved by replacing the corresponding mouse DNA sequence witha6-base DNA sequence from the human CREB1promoterthat is associated with MDD in individuals from families with recurrent, early-onset MDD (RE-MDD). In the current study, we explored the effect of the pathogenic Creb1 allele on gene expression in the mouse hippocampus, a brain region that is altered in structure and function in MDD. Mouse whole-genome profiling was performed using the Illumina MouseWG-6 v2.0 Expression BeadChip microarray. Univariate analysis identified 269 differentially-expressed genes in the hippocampus of the mutant mouse. Pathway analyses highlighted 11 KEGG pathways: the phosphatidylinositol signaling system, which has been widely implicated in MDD, Bipolar Disorder, and the action of mood stabilizers; gap junction and long-term potentiation, which mediate cognition and memory functions often impaired in MDD; cardiac muscle contraction, insulin signaling pathway, and three neurodegenerative brain disorders (Alzheimer’s, Parkinson’s, and Huntington’s Diseases) that are associated with MDD; ribosome and proteasome pathways affecting protein synthesis/degradation; and the oxidative phosphorylation pathway that is key to energy production. These findings illustrate the merit of this congenic C57BL/6 recombinant mouse as a model of RE-MDD, and demonstrate its potential for highlighting molecular and cellular pathways that contribute to the biology of MDD. The results also inform our understanding of the mechanisms that underlie the comorbidity of MDD with other disorders.
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影响因子：
14.9
作者：
Khatri P;Voichita C;Kattan K;Ansari N;Khatri A;Georgescu C;Tarca AL;Draghici S
通讯作者：
Draghici S
影响因子：
11
作者：
Li, M.;Luo, X-j;Rietschel, M.;Lewis, C. M.;Mattheisen, M.;Mueller-Myhsok, B.;Jamain, S.;Leboyer, M.;Landen, M.;Thompson, P. M.;Cichon, S.;Noethen, M. M.;Schulze, T. G.;Sullivan, P. F.;Bergen, S. E.;Donohoe, G.;Morris, D. W.;Hargreaves, A.;Gill, M.;Corvin, A.;Hultman, C.;Toga, A. W.;Shi, L.;Lin, Q.;Shi, H.;Gan, L.;Meyer-Lindenberg, A.;Czamara, D.;Henry, C.;Etain, B.;Bis, J. C.;Ikram, M. A.;Fornage, M.;Debette, S.;Launer, L. J.;Seshadri, S.;Erk, S.;Walter, H.;Heinz, A.;Bellivier, F.;Stein, J. L.;Medland, S. E.;Vasquez, A. Arias;Hibar, D. P.;Franke, B.;Martin, N. G.;Wright, M. J.;Su, B.
通讯作者：
Su, B.
影响因子：
5.1
作者：
Barco, Angel;Marie, Helene
通讯作者：
Marie, Helene
在海洋蜗牛垂直腹腔中对长期记忆的转录调节。
影响因子：
3.6
作者：
Lee YS;Bailey CH;Kandel ER;Kaang BK
通讯作者：
Kaang BK
影响因子：
--
作者：
Kessler, RC;Berglund, P;Walters, EE
通讯作者：
Walters, EE