In the hours after we die, certain cells in the human brain are still active. Some cells even increase their activity and grow to gargantuan proportions, according to new research from the University of Illinois Chicago.
In a newly published
study in the journal Scientific Reports,
the UIC researchers analyzed gene expression in fresh brain tissue — which was
collected during routine brain surgery — at multiple times after removal to
simulate the post-mortem interval and death. They found that gene expression in
some cells actually increased after death.
These ‘zombie genes’ — those that increased expression after the post-mortem
interval — were specific to one type of cell: inflammatory cells called glial
cells. The researchers observed that glial cells grow and sprout long arm-like
appendages for many hours after death.
“That glial cells enlarge after death isn’t too surprising given that they
are inflammatory and their job is to clean things up after brain injuries like
oxygen deprivation or stroke,” said Dr. Jeffrey Loeb, the John S. Garvin
Professor and head of neurology and rehabilitation at the UIC College of
Medicine and corresponding author on the paper.
What’s significant, Loeb said, is the implications of this discovery — most
research studies that use postmortem human brain tissues to find treatments and
potential cures for disorders such as autism, schizophrenia and Alzheimer’s
disease, do not account for the post-mortem gene expression or cell activity.
“Most studies assume that everything in the brain stops when the heart
stops beating, but this is not so,” Loeb said. “Our findings will be needed to
interpret research on human brain tissues. We just haven’t quantified these
changes until now.”
Loeb and his team noticed that the global pattern of gene expression in
fresh human brain tissue didn’t match any of the published reports of
postmortem brain gene expression from people without neurological disorders or
from people with a wide variety of neurological disorders, ranging from autism
to Alzheimer’s.
“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,” Loeb said.
Loeb and colleagues are at a particular advantage when it comes to studying
brain tissue. Loeb is director of the UI NeuroRepository, a bank of human brain
tissues from patients with neurological disorders who have consented to having
tissue collected and stored for research either after they die, or during
standard of care surgery to treat disorders such as epilepsy. For example,
during certain surgeries to treat epilepsy, epileptic brain tissue is removed
to help eliminate seizures. Not all of the tissue is needed for pathological
diagnosis, so some can be used for research. This is the tissue that Loeb and
colleagues analyzed in their research.
They found that about 80% of the genes analyzed remained relatively stable
for 24 hours — their expression didn’t change much. These included genes often
referred to as housekeeping genes that provide basic cellular functions and are
commonly used in research studies to show the quality of the tissue. Another
group of genes, known to be present in neurons and shown to be intricately
involved in human brain activity such as memory, thinking and seizure activity,
rapidly degraded in the hours after death. These genes are important to
researchers studying disorders like schizophrenia and Alzheimer’s disease, Loeb
said.
A third group of genes — the ‘zombie genes’ — increased their activity at
the same time the neuronal genes were ramping down. The pattern of post-mortem
changes peaked at about 12 hours.
“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,” Loeb said. “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.”
Source: https://today.uic.edu/zombie-genes-research-shows-some-genes-come-to-life-in-the-brain-after-death
Journal article: https://www.nature.com/articles/s41598-021-85801-6
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