“Zombie genes” increase activity in the brain after death
A striking new study has found gene expression can dramatically increase in some brain cells hours after a person dies. These “zombie genes” are primarily related to inflammatory activity and the researchers suggest scientists studying post-mortem brain tissue must take into account these significant changes.
We generally mark a person’s moment of death as when their heart stops beating. Many scientific studies investigating post-mortem tissue work on the assumption that everything stops when we die. However, a small but growing body of research is revealing plenty of cell activity and gene expression going on in the hours and days after a person’s death.
Fascinating recent research has discovered that a large volume of genes can switch on after an organism dies. But, much of this research has focused on animal tissue across a variety of organs. This new research focused specifically on human brain tissue and it arose out of some unusually discordant observations.
Jeffrey Loeb, corresponding author on the new research, is director of the UI Neurorepository at University of Illinois at Chicago, and his team manages a library of human brain tissue collected from consenting patients with neurological diseases.
The research team has the advantage of being able to analyze brain tissue incredibly quickly after collection. Looking at patterns of gene expression in fresh human brain tissue they noticed big differences between what they were seeing and published brain tissue gene expression data.
"We decided to run a simulated death experiment by looking at the expression of all human genes, at time points from 0 to 24 hours, from a large block of recently collected brain tissues, which were allowed to sit at room temperature to replicate the postmortem interval," explains Loeb.
The tissue Loeb and his team used in the new study came from patients with epilepsy undergoing surgery to reduce seizures. This allowed the researchers to investigate temporal changes to brain tissue gene expression from the moment of collection.
The majority of genes in the analyzed brain tissue didn’t change much over the 24-hour study period. But, a small volume of "zombie genes" actually increased activity in these post-mortem hours. These genes increasing in activity were directly linked with glial cells, a particular type of immune cell in the brain.
Loeb suggests it isn’t particularly surprising to see this kind of immune gene activity in the brain following death. After all, these cells respond directly to brain injury. But what is notable is the sheer volume of activity occurring in those hours after death. The study notes the patterns of gene expression peak around 12 hours after death but activity was observed at least 24 hours after tissue resection.
The big takeaway from this novel study is for researchers investigating human brain tissue. Loeb says these findings demand postmortem brain tissue studies take into account the significant changes that can occur in tissue after death, and researchers must try to study brain tissue closer to a person’s time of death.
"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 post-mortem interval as much as possible to reduce the magnitude of these changes," says Loeb. "The good news from our findings is that we now know which genes and cell types are stable, which degrade, and which increase over time so that results from postmortem brain studies can be better understood."
The new study was published in the journal Scientific Reports.