'Zombie' genes? Research shows some genes come to life in the brain
after death
Post-mortem changes may shed light on important brain studies

Date:
March 23, 2021
Source:
University of Illinois at Chicago
Summary:
Researchers analyzed gene expression in fresh brain tissue and found
that gene expression in some cells actually increased after death.



FULL STORY ==========================================================================
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.


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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."
This research was funded by grants from the National Institutes of Health (R01NS109515, R56NS083527, and UL1TR002003).

========================================================================== Story Source: Materials provided by
University_of_Illinois_at_Chicago. Original written by Sharon
Parmet. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Fabien Dachet, James B. Brown, Tibor Valyi-Nagy, Kunwar D. Narayan,
Anna
Serafini, Nathan Boley, Thomas R. Gingeras, Susan E. Celniker,
Gayatry Mohapatra, Jeffrey A. Loeb. Selective time-dependent
changes in activity and cell-specific gene expression in
human postmortem brain. Scientific Reports, 2021; 11 (1) DOI:
10.1038/s41598-021-85801-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/03/210323131230.htm

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