A new study by Mount Sinai researchers reveals crucial differences in RNA editing between living and postmortem brain tissues, offering fresh insights that could lead to better diagnostics and treatments for neurological disorders.
In an unprecedented study published in Nature Communications, scientists at the Icahn School of Medicine at Mount Sinai have revealed crucial differences in RNA editing between postmortem and living human brain tissues. This breakthrough could significantly influence the future of diagnostics and therapies for neurological diseases.
Insight Into Brain Development and Disease
The research team focused on adenosine-to-inosine (A-to-I) editing, one of the most common RNA modifications in the brain, which is influenced by proteins in the ADAR family. This type of RNA modification plays critical roles in neuronal maturation and brain development and has been associated with neurological disorders.
“Until now, the investigation of A-to-I editing and its biological significance in the mammalian brain has been restricted to the analysis of postmortem tissues,” Michael Breen, co-senior author of the study and assistant professor of psychiatry and genetics and genomic sciences at Icahn Mount Sinai, said in a news release. “By using fresh samples from living individuals, we were able to uncover significant differences in RNA editing activity that previous studies, relying only on postmortem samples, may have overlooked.”
Living vs. Postmortem Brain Tissues
The study revealed that RNA editing levels are significantly higher in postmortem brain tissue compared to living tissue, likely due to postmortem changes such as inflammation and hypoxia. These findings emerged from the analysis of dorsolateral prefrontal cortex (DLPFC) tissues from living individuals, obtained during neurosurgical procedures as part of the Living Brain Project, compared with matched postmortem tissues.
“We hypothesized that molecular responses to postmortem-induced hypoxic and immune responses can significantly alter the landscape of A-to-I editing,” Miguel Rodríguez de los Santos, co-first author of the study and a postdoctoral fellow in the Department of Psychiatry at Mount Sinai, said in the news release. “Studying living brain tissue provides us with a clearer picture of RNA editing biology in the human brain.”
Implications for Research and Therapy
This study marks a significant shift in understanding brain biology. It emphasizes the need to examine both living and postmortem brain tissues to gain a comprehensive perspective on RNA editing’s role in brain function and disease. These insights could usher in new diagnostic and therapeutic approaches for neurological disorders.
“Utilizing fresh brain tissue from living human donors provided us the opportunity to investigate the brain without the confounds inherent to postmortem tissue analysis,” said Alexander W. Charney, co-senior author and associate professor of psychiatry, genetics and genomic sciences, neuroscience and neurosurgery at Icahn Mount Sinai, added. “It is critical to note that our findings do not negate but instead provide missing context for using postmortem brain tissues in researching A-to-I regulation.”
Future Directions
The research team plans to delve deeper into RNA editing data to identify potential therapeutic targets for conditions such as Parkinson’s disease. They will also explore gene expression, proteomics, and multi-omics analysis within the Living Brain Project cohort.
“By harnessing the unique, transdisciplinary nature of the Living Brain Project, we can turn a cutting-edge clinical care modality like deep brain stimulation into a platform for unprecedented insight into human brain biology,” said Brian Kopell, co-first author of the study and director of the Center for Neuromodulation at Mount Sinai.
This groundbreaking research at Mount Sinai, supported by the National Institute on Aging, paves the way for enhanced understanding of brain biology and the development of innovative treatment methods for brain diseases.