Gene expressional characterization of the Dorsomedial Prefrontal Cortex in depressed and suicide victims
01/30/2020
Fanni Dóra1, 2, Éva Renner1, 3, Miklós Palkovits1, 3, Árpád Dobolyi2, 4
1 Human Brain Tissue Bank, Semmelweis University, Budapest, Hungary
2 Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary;
3 Human Brain Tissue Bank and Microdissection Laboratory, Semmelweis University, Budapest, Hungary;
4 MTA-ELTE Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Eötvös Loránd University and the Hungarian Academy of Sciences, Budapest, Hungary
Only few brain expression profiling studies provide insights into the role of genes and their potential contribution to the development of suicidal behavior related to major depression. In the human brain, the resting state network (RSN) is affected in psychiatric disorders. The expressional alterations related to depression have not been reported in the dorsomedial prefrontal cortex (DMPFC), which represents a major functionally significant component of this network. We investigated the molecular changes in relation to depression of suicide victims by RNA sequencing. Subjects were assigned into three groups: control subjects without psychiatric disorders, depressed suicide victims, and suicides without any known signs or treatments for chronic depression. RNA-seq analysis identified more than 200 genes differed in control vs suicide / depressed suicide groups. In this respect, the cluster analysis suggested that suicide and depressed suicide groups were quite similar, but both differ markedly from the control subjects. By functional enrichment analyses, we identified significant differences in more than 100 functional pathways. The oxidative phosphorylation, endocrine cannabinoid signaling and cytokine receptor pathways were over-represented in suicide victims suggesting that these processes are involved in suicidal behavior. RT-PCR was used to validate the expression of candidate genes. Results imply extensive gene expressional alterations in the DMPFC related to depression and suicidal behavior. Neurons in the DMPFC receive signal from the external and internal milieu, project to the precuneus in the parietal lobe via RSN. The precuneus is known as the control hub in the self-controlling, self-reflection and regulation of emotion and arousal. Grant support: NKFIH NAP program 2017-1.2.1-NKP-2017-00002 for ER and MP, and NKFIH-4300-1/2017-NKP_17 for AD.