Some cells in the human brain remain active even after we die. Also, specific cells expand their activities and grow to enormous portions, as per the new study from the University of Illinois, Chicago.
In a recently published research in the publication Scientific Reports, the UIC scientists examined gene expression in fresh brain membrane. It was obtained during regular brain surgery, many times after extraction to simulate the post-mortem interval and death. They discovered that gene expression in several cells developed after death.
These ‘zombie genes’ — those that grow expression after the post-mortem interval was particular to one kind of cell: inflammatory cells called glial cells. The scientists scrutinized that glial cells spread and grow long, arm-like attachments for several hours after death.
“The glial cells are inflammatory and after death, they tend to expand in the human brain. Their task is to clean up everything after brain traumas like stroke or oxygen deprivation,” said Dr. Jeffrey Loeb, head of rehabilitation and neurology and the John S. Garvin Professor at the UIC College of Medicine and author on the paper.
What’s meaningful, Loeb said, is the connections of this research– most analysis studies that use post-mortem human brain tissues to discover possible cures and medications for disorders such as Alzheimer’s disease, schizophrenia, and autism do not consider the post-mortem cell activity or gene expression.
“According to several analyses that as the heart stops pounding, everything in the brain freezes, but this is not so,” Loeb said. “Our conclusions will be required to evaluate the study on human brain tissues. We just haven’t quantified these modifications till now.”
Loeb and his partners observed that the global model of gene expression in fresh human brain tissue didn’t resemble any of the published papers of postmortem brain gene expression from people with a wide range of neurological disorders, varying from Alzheimer’s to autism or people without neurological dysfunctions.
“We conduct a simulated death trial by analyzing the expression of all human genes, at time duration from 0 to 24 hours, from a huge slab of freshly gathered brain tissues, which were placed at room temperature to replicate the postmortem interval,” Loeb said.
Loeb and his associates are at a specific lead when it comes to examining brain tissue. Loeb is executive of the UI NeuroRepository, a human brain tissue bank from patients with neurological dysfunctions who have agreed to have tissue collected and stored for analysis either during standard of care surgery to operate disorders such as epilepsy or after they die. For example, in specific surgeries to treat epilepsy, epileptic brain tissue is taken out to eliminate seizures. Not all of the tissue is required for pathological diagnosis, so some can be utilized for the study. This is the tissue that Loeb and his associates examined in their study.
They noticed that approximately 75% of the genes examined remained almost stable for 24 hours — their expression didn’t alter much. These involved genes are often related to housekeeping genes that give essential cellular functions and are usually employed in experimentation to determine the quality of the tissue. Another collection of genes, known to be existing in neurons and shown to be intricately involved in human brain activity such as thinking, seizure activity, and memory, quickly deteriorated in the hours after death. These genes are essential to scientists analyzing ailments like Alzheimer’s disease and schizophrenia, Loeb said.
The next collection of genes the ‘zombie genes’ — expanded their action only when the neuronal genes were ramping down. The pattern of post-mortem changes peaked at about 12 hours.
“Our outcomes indicate that scientists need to take into account these cellular and genetic modifications, and decrease the post-mortem interval as much as possible to overcome the extent of these modifications, it never indicates that we should stop human tissue research trials,” Loeb said.
“The important data from our discoveries is that we now know which type of cells and gene are deteriorating, which expand over time, and which are stable so that outcomes from postmortem brain studies can be thoroughly understood.”
Fabien Dachet, Kunwar Narayan, Tibor Valyi-Nagy, Gayatry Mohapatra and Anna Serafini of UIC; Nathan Boley of the University of California, Berkeley; Susan Celniker and James Brown of Lawrence Berkeley National Laboratory; and Thomas Gingeras of Cold Spring Harbor Laboratory are co-authors on the paper.
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
This research was funded by grants from the National Institutes of Health (R01NS109515, R56NS083527, and UL1TR002003).