Introduction Bipolar disorder is a mental health condition characterized by extreme mood swings, including episodes of mania and depression. Do you know that 2.4% of the global population is affected by this disorder? That is 46 million people. Understanding the biological factors behind this condition can help us find better ways to manage it. My research focuses on the role of mitochondrial dysfunction and oxidative stress in bipolar disorder.
Background Mitochondria are the powerhouses of our cells, producing the energy we need to function for everyday activities. Think of mitochondria as the battery in our cars. All the energy production for our body happens here. In people with bipolar disorder, these mitochondria are not working properly. This malfunction leads to increased oxidative stress, which means there are more harmful molecules called reactive oxygen species causing damage in the brain. This damage is particularly impactful in the prefrontal cortex, an area of the brain involved in decision-making and mood regulation.
My Research Question:
How do changes in gene expression related to mitochondrial function contribute to oxidative stress which causes Bipolar disorder?
In simple terms, the aim of my research is to understand how these mitochondrial problems and oxidative stress are connected to bipolar disorder by looking at gene activity.
My Hypothesis: If dysregulated gene expression in mitochondrial function pathways increases oxidative stress in individuals with bipolar disorder, then this oxidative stress may significantly contribute to exacerbating mood swings and other symptoms associated with the disorder."
Procedure "To explore my hypothesis, I followed these steps:
I accessed the GEO database and selected the dataset GSE23848, which compares gene expression in peripheral blood between bipolar disorder subjects and healthy controls.
I downloaded and preprocessed the data, using tools like GEO2R for differential gene expression analysis, and generated visual summaries such as box plots and volcano plots.
I used bioinformatics tools like KEGG pathway and Gene Ontology to explore pathways related to mitochondrial function and oxidative stress, identifying enriched pathways with dysregulated genes.
I employed String DB to investigate protein-protein interaction networks among these genes, visualizing and analyzing the interactions to understand functional relationships.
I validated my findings with additional resources like UCSC Browser and GeneCards, developing specific conclusion based on observed gene expression patterns and pathway analyses.
Data Analysis: From this GEO2R dataset and the associated graphs, I identified the genes that are upregulated and downregulated. Positive logFC values indicate that the gene is upregulated, while negative logFC values indicate that the gene is downregulated.
Next, I selected all the genes from the dataset and input them into STRING DB to determine the interactions between these genes. I focused on the pathways "mitochondrial respirasome" and "aerobic ETC" because they exhibited the greatest strength and the lowest false discovery rate among the genes related to bipolar disorder.
I then noted down the highlighted genes and searched the GEO database to determine if each gene is upregulated or downregulated. Lastly, I investigated the implications of gene upregulation and downregulation, including the potential causes and effects on bipolar disorder.
Results Our analysis showed that certain genes involved in the aerobic electron transport chain, such as COX15, COX6C, and ubiquinone oxidoreductase, were more active in people with bipolar disorder. This increased activity leads to higher levels of reactive oxygen species, causing oxidative stress. Additionally, the activity of a gene called SDHD was decreased, which further disrupts cellular balance and worsens oxidative damage.
Discussion These findings suggest that mitochondrial dysfunction and oxidative stress play a significant role in bipolar disorder. By targeting these pathways, we might be able to develop new treatments that help manage the condition more effectively.
Conclusion In summary, our research highlights the importance of mitochondrial function and oxidative stress in bipolar disorder. Oxidative stress damages cell structure and proteins largely in the prefrontal cortex, leading to many anxiety and depression-induced illnesses. By understanding these mechanisms better, we can work towards new diagnostic tools and therapies to improve the lives of those affected by this condition.
Future Directions Looking ahead, further studies are needed to delve deeper into these mechanisms. We aim to investigate specific ways to reduce oxidative stress and develop targeted treatments to improve outcomes for people with bipolar disorder.
Acknowledgments I'd like to thank my mentors, funding sources, and everyone who supported this research. For more detailed information, please refer to our list of references.
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