You would think that once a human is dead, the body would be done doing things; without blood circulation and air, the inner systems would quickly become exhausted. But because of some weird quirk of biology, there are things like the living dead – living cells, at least, in a done and dusted body.
Some cells in the human brain increase their activity even after we die. These ‘zombie’ cells speed up their gene expression and courageously continue to try to perform their vital tasks, as if someone forgot to tell you that they are now redundant.
University of Illinois neurologist Jeffrey Loeb and colleagues watched as these cells stubbornly sprouted new tentacles and engaged in chores hours after they died.
“Most studies assume that everything in the brain stops when the heart stops beating, but it doesn’t,” Loeb said. “Our findings will be needed to interpret research on human brain tissue. We just haven’t quantified these changes so far.”
Much of the information we have about brain disorders such as autism, Alzheimer’s and schizophrenia comes from experiments conducted on brain tissue after death; this approach is crucial in the search for treatments, as animal models for brain studies often cannot be translated to us.
Typically, this work is done on tissues from people who died more than 12 hours ago. By comparing gene expression in fresh brain tissue (removed as part of epilepsy surgery in 20 patients) with previously mentioned brain samples from deceased people, Loeb and team found striking differences that were not age or disease specific.
They used gene expression data, which they later confirmed by examining brain tissue histology, to understand cell-specific activity changes over time since death, at room temperature.
While most of the gene activity remained stable over the 24 hours the team documented, neuronal cells and their gene activity were rapidly depleted. Most notable, however, are glial cells increased gene expression and processes.
Cells come to life after the death of the human brain. (Dr. Jeffrey Loeb / UIC)
While this is surprising at first, it actually makes a lot of sense, as glial cells, such as waste-eating microglia and astrocytes, are put into action when something goes wrong. And dying is about as ‘wrong’ as living things can go.
“It is not surprising that glial cells get bigger after death, since they are anti-inflammatory and their job is to clear things up after brain injuries such as oxygen deprivation or stroke,” said Loeb.
The team then showed that the RNA expressed by genes itself does not change within 24 hours of death, so indeed any change in the amount must be due to the continuation of biological processes.
“The full gene expression of freshly isolated human brain samples provides an unprecedented picture of the genomic complexity of the human brain, due to the preservation of so many different transcripts that are no longer present in post-mortem tissues,” the researchers wrote in their paper.
This has huge implications for both past and current studies using brain tissue to understand diseases involving immune responses – like these “ zombie ” glial cells that swell as they vainly devour surrounding bits of dying brain.
However, after 24 hours, these cells also collapsed and were indistinguishable from the degraded tissue surrounding them.
“Researchers need to account for these genetic and cellular changes and shorten the post-mortem interval as much as possible to reduce the magnitude of these changes,” explains Loeb.
“The good news of our findings is that we now know which genes and cell types are stable, which degrade, and which increase over time, so that the results of post-mortem brain studies can be better understood.”
Even at death, we biological entities are never completely static.
This research is published in Scientific reports