Gene expression effects of lithium and valproic acid in a serotonergic cell line

被引:13
作者
Balasubramanian, Diana [1 ]
Pearson, John F. [1 ,2 ]
Kennedy, Martin A. [1 ]
机构
[1] Univ Otago, Carney Ctr Pharmacogen, Dept Pathol & Biomed Sci, Christchurch, New Zealand
[2] Univ Otago, Biostat & Computat Biol Unit, Christchurch, New Zealand
关键词
gene expression; mood stabilizer; pharmacogenomics; RNA-Seq; valproic acid; DORSAL RAPHE NUCLEUS; BRAIN MESSENGER-RNA; MATRIX METALLOPROTEINASES; MOOD STABILIZERS; BIPOLAR DISORDER; DIFFERENTIATION; PHARMACOLOGY; POLYMORPHISM; ACETYLATION; DEPRESSION;
D O I
10.1152/physiolgenomics.00069.2018
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. however, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log 2 fold change >= 1.0; i.e., odds ratio of >= 2.at false discovery rate <5%), but only two genes (Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B), and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix remodeling, cell adhesion, and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into potential therapeutic actions of the commonly used mood stabilizer drugs.
引用
收藏
页码:43 / 50
页数:8
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