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."
Reference:
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