Researchers discover "Zombie Genes" in the brain that come to life after death

Imagine watching your favorite medical drama. The surgeons are scrambling to save the patient, who is lying on the table, cut open and under the influence of anesthesia. Just before the surgeon can finish their beautifully-written speech about how they endured medical school for this very moment, they are interrupted by a loud, flatline sound. Suddenly, all is silent and the scene cuts to black. Everyone knows that a heart stops beating when a person dies, but what about the brain?

It seems that there may be a missing piece of the puzzle in understanding the phenomena behind brain activity after heart death. Last week, researchers from the University of Illinois at Chicago (UIC) discovered a certain subset of microglial cells with increased gene expression during the hours postmortem. Named after the undead corpses from popular culture and media, these genes are known as “zombie genes.”

Microglial cells are the immune cells local to the human brain, as well as the central nervous system (CNS). Their main functions involve removing damaged neurons and infections from the CNS, sometimes after brain injuries such as strokes. For this very reason, some neurologists are not surprised that microglial cells show increased gene expression postmortem.

The researchers used fresh brain tissue samples collected from routine brain surgery procedures, removing them to mimic the postmortem interval (PMI). From this, they observed the changes in gene expression between zero and 24 hours after the induced death and were able to witness microglial cells growing appendages in the brain.

In fact, the postmortem brain was found to have an entirely different pattern of human gene transcription. Along with the increased microglial expression, the researchers found a rapid decline in neuronal gene expression that lasted at least 24 hours. This was confirmed histologically by observed neuron degeneration and glial cell outgrowth.

Dr. Jeffrey Loeb, head of neurology and rehabilitation at the UIC College of Medicine and the head of this study, believes that this has important implications. Postmortem brain tissues have been analyzed by many scientists in the past to find treatments and potential cures for neurological disorders including autism, schizophrenia, and even Alzheimer’s disease. However, many do not account for postmortem genetic expression or even cellular activity in the brain, which could alter the conclusions drawn from research on these treatments.

Loeb and his team noticed that the pattern observed in their study was nothing like the already-published findings about neurological decline within brains affected by neurological disorders. By using fresh brain tissue samples, Loeb and his team did not have to worry about RNA degradation, which would usually occur if the samples were older. As a result, the total amount of RNA per milligram of tissue was constant over the course of the study, though Loeb and his team claim that this is because the increase in glial cells compensates for the neuron degradation.

Loeb states that "Our findings don't mean that we should throw away human tissue research programs, it just means that researchers need to take into account these genetic and cellular changes, and reduce the postmortem interval as much as possible to reduce the magnitude of these changes.” He says that by knowing which cells degenerate postmortem, and which genes are stable, postmortem studies on all types of brain tissue can be better understood.