Christensen Trine, Jensen Line, Bouzinova Elena V, Wiborg Ove
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
PLoS One. 2013 Dec 5;8(12):e80666. doi: 10.1371/journal.pone.0080666. eCollection 2013.
This study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level.
Rat whole genome expression chips (Affymetrix) were used to detect gene expression regulations in the lateral habenula of rats subjected to chronic mild stress (mild stressors exchanged twice a day for 8 weeks). Some rats received antidepressant treatment during fifth to eights week of CMS. The lateral habenula gene expression profile was studied through the gene ontology and signal pathway analyses using bioinformatics. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine the expression of the Fcrla, Eif3k, Sec3l1, Ubr5, Abca8a, Ankrd49, Cyp2j10, Frs3, Syn2, and Znf503 genes in the lateral habenula tissue.
In particular we found that stress and antidepressant treatment affected intracellular cascades like growth factor receptor signaling, G-protein-coupled receptor signaling, and Wnt signaling - processes involved in the neuroplastic changes observed during the progression of depression and antidepressant treatment.
The present study suggests an important role of the lateral habenula in the development of depression-like conditions and correlates to previous studies demonstrating a significant role of the lateral habenula in depressive-like conditions and antidepressant treatment.
本研究在全基因组水平系统地研究了慢性轻度应激对外侧缰核的影响以及外侧缰核对抗抑郁治疗的反应。
使用大鼠全基因组表达芯片(Affymetrix)检测遭受慢性轻度应激(轻度应激源每天更换两次,持续8周)的大鼠外侧缰核中的基因表达调控。部分大鼠在慢性轻度应激的第5至8周接受抗抑郁治疗。通过生物信息学的基因本体论和信号通路分析研究外侧缰核基因表达谱。采用实时定量聚合酶链反应(RT-PCR)验证芯片结果,并测定外侧缰核组织中Fcrla、Eif3k、Sec3l1、Ubr5、Abca8a、Ankrd49、Cyp2j10、Frs3、Syn2和Znf503基因的表达。
我们特别发现,应激和抗抑郁治疗会影响细胞内级联反应,如生长因子受体信号传导、G蛋白偶联受体信号传导和Wnt信号传导——这些过程参与了在抑郁症进展和抗抑郁治疗过程中观察到的神经可塑性变化。
本研究表明外侧缰核在抑郁症样状态的发生发展中起重要作用,这与之前的研究相关,之前的研究表明外侧缰核在抑郁症样状态和抗抑郁治疗中起重要作用。