Identification of differentially expressed genes in hebanula's cells of people who commited suicide and were diagnosed with clinical depression
Clinical Depression is a psychiatric ilness with its main symptoms being bad mood, low self-esteem and loss of productivity. Main symptoms are also changes in sleep schedule, stress and unexplainable body pains Causes that could lead to clinical depresson vary and it is difficult to be orientated. Lead factors who have been verified are the patient's personallity, labour and lonelyniess. Some different and less psychological factors are alcohol and drugs, family history and serious ilnesses that could lead to death like cancer or serious brain injuries. It has been found that stress and depression activate factor that are responsible for the death of cells of the nervous system by hyperoxidization of the cell membrane's lipids from reactive oxygen species (ROS) and by apoptosis. Many antidepressants focus on protecting neurons from ROS and apoptosis by enhasing protective mechanisms. At least half of the patients diagnosed with clinical depression have suicidal thoughts. In the last years, the cases of suicides and patients with clinical depression have risen. Even from my personal and social relationships I have observed that a lot of people face personal problems. This may be cause due to modern society's way of living, which spends time of peoples' days in psychotic patterns. So, all these previous statements have made me want to look more into the biological mechanism behind clinical depression and suicide.
By using Gene Expression Omnibus (GEO), I chose the following data series: Kim HJ, Yoo H, Kim JY, Yang SH, Lee HW, Lee HJ, Son GH, Kim H. Postmortem gene expression profiles in the habenulae of suicides: implication of endothelial dysfunction in the neurovascular system. Mol Brain. 2022 May 25;15(1):48. doi: 10.1186/s13041-022-00934-7. PMID: 35614468; PMCID: PMC9134578. This data series is an analysis of gene expression of cells of the brain's hebanula of 10 people who were all diagnosed with clinical depression and commited suicide, compared with the gene expression of 10 healthy alive people. In order to start my analysis with GEO2R, I separated the samples in two groups:
- Control -> for the healthy people
- Suicide -> for the people with clinical depression
GEO2R provided automatically the code for the analysis which is located in the file "R-code" of this repository. This code was then coppied in RStudio. In order for it to be working, I had to download the packages:
- GEOquery
- limma
- umpa
- BioGenerics
From the results of the analysis, 5 genes were selected with the lowest pvalue. From the genebank accession number, I was able to find the genes' names.
| GeneBank accession number | Gene Name |
|---|---|
| NM_017705.4 | Homo sapiens progestin and adipoQ receptor family member 5 (PAQR5), transcript variant 2, mRNA |
| NM_021127.3 | Homo sapiens phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), transcript variant 6, mRNA |
| NM_020997.4 | Homo sapiens left-right determination factor 1 (LEFTY1), mRNA |
| NM_005346.6 | Homo sapiens heat shock protein family A (Hsp70) member 1B (HSPA1B), mRNA |
| NM_005797.4 | Homo sapiens myelin protein zero like 2 (MPZL2), transcript variant 1, mRNA |
This gene codes the protein PAQR5, which is a membrane receptor of progesterone and antiponectin. Progesterone in women is mainly responsible for preparing the uterus in order to receive and support zygote's developement. Antiponectin is secreated from fatty cells and regulates the metabolism of lipids and glucose in the liver, the muscle tissue and other organs. It should be noted that these hormones activate a G-protein pathway. For this specific analysis, I looked for different roles of this hormones in order to connect their function with the nervous system. It should be said at this point that all samples were from male humans, which is not normal with the higher expression of PAQR5, as progesterone characterizes the female organism. Progesterone plays a role too in functions such as regulating the brain's activity, mood homeostasis and libido. These psychological processes may be related with clinical depression.
This gene codes the PMAIP1 protein, which has a 54 amino-acid sequence and has a key role in cell apoptosis. It is mostly located in the mitochondria It's functions are mainly caspases activation, who start the apoptosis mechanism. It also takes place in TP53's apoptotic pathway after cell radiation expose. The way with which PMAIP1 contributes in the activation of apoptosis is mainly by deactivating proteins who support cellular survival. To be more specific, it is responsible for degradation of MCL1, a protein who inhibits apoptosis. This way, just by interacting with it, PMAIP1 stops MCL1 from interacting with and preventing the function of pro-apoptotic proteins. The results of the analysis showed that PMAIP1's expression was higher in the suicide samples, indicating the probability of neurones undergoing apoptosis.
This gene codes the protein LEFTY1, who is consisted by 366 amino acids. It is located in the intracellular space and regulates the organs' symmetry. This symmetry is based on the left-right axis of the body while developement. The big interest in this specific example is that hebanula is physiologically asymmetric. In humans, hebanula has a differential sub-unit concentration, activity and metabolism, giving it it's particular geometry. LEFTY1's expression was higher in the suicide samples and may be capable of producing disfunction, as it indicates that hebanula was getting to be more symmetric, which could possibly be pathogenic.
This gene codes a chaperone, the protein HSPA18. Chaperones are responsible for protecting the cellular proteome from stress and damage. They also help on regulating correct protein folding. HSPA18 is consisted by 641 amino acids and located in the cytoplasm. From IntAct there were observed interactions of this protein with mainly other chaperones and MAP-kinases. MAP-kinases are pro- or anti- apoptotic, based on the stimuli and the cell type.