GABA和谷氨酸传导通路在抑郁症患者大脑前额叶皮层的改变

发布时间：2018-10-26 17:58

【摘要】：背景:抑郁症是一类很常见并且可以造成严重后果的精神疾病。自杀行为是典型的抑郁症状之一,可以贯穿整个抑郁症的发病阶段。老年痴呆患者中,有高达50%的患者合并抑郁症状。先前对于抑郁症患者群的研究表明神经递质Y-氨基丁酸(GABA)和谷氨酸(Glutanate)及其相关传导通路在抑郁症患者的前额叶皮层发生改变与其发病机制有关。但这些研究对于抑郁症患者未进行良好细致的分类,因此,对于不同抑郁症状表现的患者群其GABA和谷氨酸相关的发病机制我们还知之甚少。目的:研究GABA和谷氨酸传导通路在抑郁症患者大脑前额叶皮层的作用。方法:该研究运用三个不同的抑郁症人群数据库,通过实时荧光定量PCR技术在人脑前额叶皮层扣带回前部(anterior cingulate cortex,ACC)和前额叶皮层背外侧区(dorsolateral prefrontal cortex,DLPFC)对GABA和谷氨酸传导通路上的相关受体、转运体以及代谢酶进行研究。结果:通过对33个目的基因的检测,我们发现在非自杀型老年抑郁症患者中,前额叶皮层扣带回前部中GABRB2和PSD-95两个分子的mRNA转录水平较对照组显著降低,但在前额叶皮层背外侧区中未见任何基因转录水平发生改变。在自杀型抑郁症患者中,其前额叶皮层扣带回前部中的GABA和谷氨酸介导的传导通路上的13个基因其转录水平相对非自杀型抑郁症和对照组显著升高,表明了在扣带回前区GABA和谷氨酸功能不良与自杀的相关性远超过与抑郁本身的相关性。此外在抑郁型老年痴呆病人中,GABRA5和GABBR2 mRNA转录水平的前额叶皮层背外侧区相对非抑郁型老年痴呆患者发生降低,且在抑郁型老年痴呆中,VGluTl mRNA的转录水平与抑郁症严重程度呈正相关。结论:在不同症状表现的抑郁症中,大脑前额叶的GABA和谷氨酸传导途径呈现完全不同的功能障碍表现,并且功能不良与自杀的相关性远超过与抑郁本身的相关性。
[Abstract]:Background: depression is a common mental disorder with serious consequences. Suicidal behavior is one of the typical depressive symptoms and can run through the whole stage of depression. As many as 50% of patients with Alzheimer's disease have depressive symptoms. Previous studies in patients with depression have shown that the changes of neurotransmitters Y- aminobutyric acid (GABA), glutamate (Glutanate) and their related transduction pathways in the prefrontal cortex of depression patients are related to the pathogenesis of depression. However, these studies do not have a good classification of depression patients, so we know little about the pathogenesis of GABA and glutamate in patients with different symptoms of depression. Aim: to study the role of GABA and glutamate transduction pathway in prefrontal cortex of depression patients. Methods: three different depressive population databases were used in this study using real-time fluorescence quantitative PCR technique in the prefrontal cortex cingulate gyrus (anterior cingulate cortex,ACC) and prefrontal cortex dorsolateral area (dorsolateral prefrontal cortex,. DLPFC was used to study the receptors, transporters and metabolic enzymes in GABA and glutamate transduction pathway. Results: by detecting 33 target genes, we found that the mRNA transcription levels of GABRB2 and PSD-95 molecules in the prefrontal cortex cingulate gyrus were significantly lower in non-suicidal elderly depression patients than in the control group. However, no changes in gene transcription were observed in the dorsolateral prefrontal cortex. In patients with suicidal depression, the transcription levels of 13 genes in the prefrontal cortex cingulate gyrus GABA and glutamate mediated conduction pathway were significantly higher than those in non-suicide depression and control groups. This suggests that GABA and glutamate dysfunction in the anterior cingulate gyrus are more associated with suicide than with depression itself. In addition, GABRA5 and GABBR2 mRNA transcription levels in the dorsolateral prefrontal cortex were significantly lower in depressive Alzheimer's patients than in non-depressive dementia patients, and in depressive Alzheimer's disease. The transcriptional level of VGluTl mRNA was positively correlated with the severity of depression. Conclusion: the GABA and glutamate conduction pathways in prefrontal lobe of brain present completely different dysfunction in different symptoms of depression, and the correlation between dysfunction and suicide is far greater than that with depression itself.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R749.4

【相似文献】