A recent study has shown how challenging death can be for a living brain. Scientists have observed a series of effects as oxygen levels drop and the DNA makes its final efforts to save the organism.

Researchers compared post-mortem brain tissue with samples from living patients. For the first time, they found significant differences in how RNA strands are modified. The study was conducted by the Icahn School of Medicine at Mount Sinai in New York. It focused on how specific base codes in RNA are changed after death. In living brains, adenosine (A) is often swapped with inosine (I) in messenger RNA and this process is called A-to-I editing.

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Image Source: Brainline.org

Genomicist Michael Breen spoke to Science Alert, "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. 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."

Challenges of Studying the Brain: Postmortem vs. Living Samples

To create functional proteins, genes encoded by DNA need to be copied into different formats based on RNA. These RNA strands, which contain amino acid building blocks, can then translate these 'messengers' into proteins. This process involves transcription and translation, and has been a crucial part of evolution for billions of years.

Some species, like some cephalopods, have advanced RNA editing to a new level, like rewriting their own genetic instructions for their brains. However, the study pointed out a major drawback in using post-mortem samples.

Lead author Miguel Rodríguez de los Santos, a molecular biologist at Mount Sinai, said, "We hypothesised that molecular responses to postmortem-induced hypoxic and immune responses can significantly alter the landscape of A-to-I editing. This can lead to misunderstandings about RNA editing in the brain if we only study postmortem tissues."

Despite these challenges, co-senior author Alexander Charney, a physician-scientist at Mount Sinai, highlighted the importance of their findings. He said, "It is critical to note that our findings do not negate but instead provide missing context for using postmortem tissues in researching A-to-I regulation. Understanding these differences helps improve our knowledge of brain function and disease through the lens of RNA editing modifications, which can potentially lead to better diagnostic and therapeutic approaches."

This study shows the complex processes that occur in the brain at the time of death and highlights the importance of using living samples for accurate research. The differences in RNA editing between living and post-mortem samples could lead to a better understanding of brain function and disease, thereby improving diagnostic and therapeutic strategies.

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