Researchers have found that genes in cells in recently harvested brain tissue remained active for up to 24 hours – and some ‘zombie’ genes even increased their expression.
Using recently harvested brain tissue as a surrogate for actual death, the researchers investigated the activity of genes.
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, noticed along with his team that the pattern of gene expression in fresh human brain tissue differed from 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 zero 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,” Dr Loeb said.
They found that some ‘zombie’ genes were more expressed after the simulated death. These were specific to glial cells, which have an inflammatory role. The researchers observed that these cells continued to grow 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 Loeb.
Dr Loeb is director of the UI NeuroRepository, which preserves human brain tissues from patients with neurological disorders who gave their consent to use their tissue after death, or during surgery to treat disorders such as epilepsy, where some brain tissue is removed to treat the condition in lesionectomy. This procedure involves removing structural brain lesions — typically malformations of cortical development, low-grade neoplasms, or vascular malformations. Some of the tissue harvested through these various means can be used for research, as in this study.
About 80% of genes, many of which are involved in cellular ‘housekeeping’ activities, kept functioning up to 24 hours after death. Another group of genes involved in cognition and seizure control faded within a few hours of death. These are important to the study of schizophrenia and Alzheimer’s disease, according to Dr Loeb.
The ‘zombie’ genes ramped up activity as the others were winding down, with these changes peaking at 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,” Dr 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: Medical Xpress
Journal information: Fabien Dachet et al. Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain, Scientific Reports (2021). DOI: 10.1038/s41598-021-85801-6
