Farhang Sara, Barar Jaleh, Fakhari Ali, Mesgariabbasi Mehran, Khani Sajjad, Omidi Yadollah, Farnam Alireza
Clinical Psychiatry Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
Synapse. 2014 Sep;68(9):387-93. doi: 10.1002/syn.21746. Epub 2014 Apr 29.
The current study is based on the "approach-withdrawal" theory of emotional regulation and lateralization of brain function in rodents, which has little been studied. The aim was to indentify asymmetry in hemispheric genes expression during depression. Depressive-like symptoms were induced in rats using chronic mild stress protocol. The sucrose consumption test was performed to identify the anhedonic and stress-resilient rats. After decapitation, RNA was extracted from frontotemporal cortex of both hemispheres of anhedonic and stress-resilient rats. The pattern of gene expression in these samples was compared with controls by real-time polymerase chain reaction. A linear mixed model analysis of variance was fitted to the data to estimate the effect of rat line. From the total of 30 rats in the experimental group, five rats were identified to be anhedonic and five were stress-resilient, according to the result of sucrose-consumption test. BDNF and NTRK-3 were expressed at significantly lower levels in the right hemisphere of anhedonic rats compared with stress-resilient rats. No significant difference was found between left hemispheres. Hemispheric asymmetry in the level of gene expression was only observed for the BDNF gene in stress-resilient rats, upregulated in right hemisphere compared with the left. Expression of NTRK3, HTR2A, COMT, and SERT was not lateralized. There was no significant asymmetry between hemispheres of anhedonic rats. This study supports the evidence for the role of genes responsible for neural plasticity in pathophysiology of depression, emphasizing probable hemispheric asymmetry at level of gene expression.
当前的研究基于啮齿动物情绪调节的“趋近-回避”理论以及大脑功能的偏侧化,而这方面此前鲜有研究。其目的是确定抑郁症期间半球基因表达的不对称性。使用慢性轻度应激方案在大鼠中诱导出类似抑郁的症状。进行蔗糖消耗试验以识别快感缺失和应激适应力强的大鼠。断头后,从快感缺失和应激适应力强的大鼠双侧半球的额颞叶皮质中提取RNA。通过实时聚合酶链反应将这些样本中的基因表达模式与对照组进行比较。对数据进行线性混合模型方差分析以估计大鼠品系的影响。根据蔗糖消耗试验的结果,在实验组的30只大鼠中,有5只被确定为快感缺失,5只应激适应力强。与应激适应力强的大鼠相比,快感缺失大鼠右半球中脑源性神经营养因子(BDNF)和神经营养酪氨酸激酶受体3(NTRK-3)的表达水平显著较低。左半球之间未发现显著差异。仅在应激适应力强的大鼠中观察到BDNF基因表达水平的半球不对称性,与左半球相比,右半球上调。NTRK3、5-羟色胺受体2A(HTR2A)、儿茶酚-O-甲基转移酶(COMT)和5-羟色胺转运体(SERT)的表达没有偏侧化。快感缺失大鼠的半球之间没有显著的不对称性。这项研究支持了负责神经可塑性的基因在抑郁症病理生理学中作用的证据,强调了基因表达水平可能存在的半球不对称性。