Postmortem changes may inform important brain studies – sciencedaily

In the hours following our death, some human brain cells are still active. Some cells even increase their activity and reach gargantuan proportions, according to new research from the University of Illinois at Chicago.

In a study recently published in the journal Scientific reports, UIC researchers analyzed gene expression in fresh brain tissue – which was collected during routine brain surgery – several times after removal to simulate the postmortem interval and death. They found that gene expression in some cells actually increased after death.

These “zombie genes” – the ones that increased expression after the postmortem interval – were specific to one type of cell: inflammatory cells called glial cells. Researchers observed that glial cells develop and grow long, arm-like appendages for many hours after death.

“The fact that glial cells enlarge after death is not too surprising given that they are inflammatory and their job is to clean things up after brain damage like oxygen deprivation or a stroke. “said Dr Jeffrey Loeb, Professor John S. Garvin and Head of Neurology and Rehabilitation at UIC College of Medicine and corresponding author on the article.

What’s important, Loeb said, are the implications of this finding – most research studies that use postmortem human brain tissue to find potential treatments and cures for disorders such as autism, schizophrenia and Alzheimer’s disease, ignore postmortem gene expression. or cellular activity.

“Most studies assume that everything in the brain shuts down when the heart stops beating, but it doesn’t,” Loeb said. “Our findings will be needed to interpret human brain tissue research. We simply haven’t quantified these changes so far.”

Loeb and his team noticed that the overall pattern of gene expression in fresh human brain tissue does not match any of the published reports on postmortem brain gene expression from people without neurological disorders or from people with a wide variety. neurological disorders, ranging from autism. to Alzheimer’s disease.

“We decided to conduct a mock death experiment by examining the expression of all human genes, at 0-24 hour time points, from a large block of newly collected brain tissue, which was allowed to rest. at room temperature to reproduce the post-mortem. interval, ”Loeb said.

Loeb and his colleagues have a particular advantage when it comes to studying brain tissue. Loeb is Director of UI NeuroRepository, a bank of human brain tissue from patients with neurological disorders who have consented to tissue being collected and stored for research either after death or during surgery. standard to treat disorders such as epilepsy. For example, in some surgeries to treat epilepsy, epileptic brain tissue is removed to help rule out seizures. Not all tissues are required for pathological diagnosis, so some can be used for research. This is the fabric that Loeb and his colleagues analyzed in their research.

They found that about 80% of the genes analyzed remained relatively stable for 24 hours – their expression did not change much. These included genes often called housekeeping genes that provide basic cell functions and are commonly used in research studies to show tissue quality. Another group of genes, known to be present in neurons and shown to be closely involved in human brain activity such as memory, thinking and seizures, rapidly degraded within hours. followed 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 as the neural genes decreased. The pattern of postmortem changes peaked at about 12 hours.

“Our results do not mean that we should abandon research programs on human tissue, it just means that researchers must take into account these genetic and cellular changes, and reduce the post-mortem interval as much as possible to reduce them. ‘magnitude. changes, ”Loeb said. “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. “

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

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

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