Here’s some fun news: After you die, you’re not completely dead. In a new study, scientists from the University of Illinois–Chicago reveal that some genes express more actively in the human brain after death.
How do these“zombie genes” still hang around, exactly? The answer is a combination of common sense and surprise.
To study the postmortem brain, researchers collected brain tissue samples from brain surgery patients. In Scientific Reports, they write:
“Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval.”
The scientists say they were motivated by trying to close the gap between research studies of brain issues and the living human brains we want to eventually treat.“Research in animal models that aim to understand fundamental disease processes and develop new treatments for human disorders often fail to translate back to humans in clinical trials,” they explain.
But available human brain tissue isn’t any better:
“For a majority of neuropsychiatric disorders including Alzheimer’s disease, Autism, and Schizophrenia, only postmortem tissues are available. Given the importance of these studies we examined the fidelity of overall gene expression between fresh and postmortem human brain tissues for a number of brain disorders with a central focus on activity-dependent genes that are likely involved in higher cognitive human brain function.”
Basically, if our only options are these fairly subpar analogs to the living human brain, we’d better understand as well as possible how different the postmortem brain really is. And to do that, the scientists compared the freshest possible brain tissue to traditional postmortem brain tissue.
They found a totally different landscape of expressed genes, with neuronal ones falling in activity while glial genes rose to compensate:
“We found that 1427 genes could be clustered. One cluster of 317 rapidly declining genes was predicted to be neuronal and strongly overlapped with the activity-dependent genes. A second cluster of 474 genes was predicted to be glial, including astrocytes and microglia. Remarkably, as the neuronal cell cluster rapidly fell, there was a reciprocal and dramatic increase in the expression of the glial cell cluster.”
What explains this“zombie gene” activity? In a statement, corresponding author Jeffrey Loeb explains the sensible answer:“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,” he explains.
In a way, the glial genes represent a cleanup crew that’s only activated after a messy incident—like brain surgery.
While 80 percent of genes stayed stable over time, the neuronal and glial genes represent the other 20 percent. The glial“zombie” genes peaked their increased activity after about 12 hours on average.
Understanding the brain’s chemical signatures is key for scientists who are trying to find ways to cure devastating brain diseases like Huntington’s. This research was boosted by a great resource the study team has: the University of Illinois neurorepository, a collection of samples of brain tissue samples that Loeb chairs. The samples in this study were from patients with epilepsy and other brain diseases.