“Zombie” Cells? Research Shows Some Genes Come to Life in the Brain After We Die

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Zombie Cells

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Post-mortem modifications might clarify crucial brain research studies.

In the hours after we pass away, particular cells in the human brain are still active. Some cells even increase their activity and grow to gigantic percentages, according to brand-new research study from the University of Illinois Chicago.

In a freshly released research study in the journal Scientific Reports, the UIC scientists evaluated gene expression in fresh brain tissue — which was gathered throughout regular brain surgical treatment — at numerous times after elimination to replicate the post-mortem period and death. They discovered that gene expression in some cells really increased after death.

These ‘zombie genes’ — those that increased expression after the post-mortem period — specified to one kind of cell: inflammatory cells called glial cells. The scientists observed that glial cells grow and grow long arm-like appendages for numerous 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,” stated Dr. Jeffrey Loeb, the John S. Garvin Professor and head of neurology and rehab at the UIC College of Medicine and matching author on the paper.

What’s considerable, Loeb stated, is the ramifications of this discovery — most research study studies that utilize postmortem human brain tissues to discover treatments and prospective remedies for conditions such as autism, schizophrenia and Alzheimer’s illness, do not represent the post-mortem gene expression or cell activity.

Zombie Cells

‘Zombie’ cells come to life after the death of the human brain. Credit: Dr. Jeffrey Loeb/UIC

“Most studies assume that everything in the brain stops when the heart stops beating, but this is not so,” Loeb stated. “Our findings will be needed to interpret research on human brain tissues. We just haven’t quantified these changes until now.”

Loeb and his group discovered that the international pattern of gene expression in fresh human brain tissue didn’t match any of the released reports of postmortem brain gene expression from individuals without neurological conditions or from individuals with a wide array of neurological conditions, varying 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 stated.

Jeffrey Loeb

Jeffrey Loeb. Credit: Jenny Fontaine/UIC

Loeb and coworkers are at a specific benefit when it concerns studying brain tissue. Loeb is director of the UI NeuroRepository, a bank of human brain tissues from clients with neurological conditions who have actually granted having actually tissue gathered and kept for research study either after they pass away, or throughout requirement of care surgical treatment to deal with conditions such as epilepsy. For example, throughout particular surgical treatments to deal with epilepsy, epileptic brain tissue is eliminated to assist remove seizures. Not all of the tissue is required for pathological medical diagnosis, so some can be utilized for research study. This is the tissue that Loeb and coworkers evaluated in their research study.

They discovered that about 80% of the genes evaluated stayed reasonably steady for 24 hours — their expression didn’t alter much. These consisted of genes frequently described as housekeeping genes that supply standard cellular functions and are frequently utilized in research study studies to reveal the quality of the tissue. Another group of genes, understood to be present in nerve cells and revealed to be elaborately associated with human brain activity such as memory, believing and seizure activity, quickly broken down in the hours after death. These genes are necessary to scientists studying conditions like schizophrenia and Alzheimer’s illness, Loeb stated.

A 3rd group of genes — the ‘zombie genes’ — increased their activity at the exact same time the neuronal genes were ramping down. The pattern of post-mortem modifications 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 stated. “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: “Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain” by Fabien Dachet, James B. Brown, Tibor Valyi-Nagy, Kunwar D. Narayan, Anna Serafini, Nathan Boley, Thomas R. Gingeras, Susan E. Celniker, Gayatry Mohapatra and Jeffrey A. Loeb, 23 March 2021, Scientific Reports.
DOI: 10.1038/s41598-021-85801-6

Fabien Dachet, Tibor Valyi-Nagy, Kunwar Narayan, Anna Serafini and Gayatry Mohapatra of UIC; James Brown and Susan Celniker of Lawrence Berkeley National Laboratory; Nathan Boley of the University of California, Berkeley; and Thomas Gingeras of Cold Spring Harbor Laboratory are co-authors on the paper.

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