In a new study, researchers analysed gene expression patterns in fresh brain tissue, revealing that some ‘zombie’ cells increase their activity and grow after death.
The results from studies involving animal models, regarding our understanding of disease processes and treatment development, often fail to translate back into humans during clinical trials. As a result, researchers often use human tissue to improve translation and validate future therapeutic targets. This is particularly relevant for the study of the human brain. In some brain disorders, including epilepsy, experts can isolate fresh tissue as part of a patient’s surgical treatment and use it for research. In contrast, in the majority of neuropsychiatric disorders, including Alzheimer’s disease, autism and schizophrenia, only post-mortem tissues are available. Currently, most research studies that use post-mortem human brain tissue do not account for post-mortem gene expression or cell activity.
In this study, published in Scientific Reports, researchers examined gene expression patterns between fresh and post-mortem human brain tissues for a range of brain disorders. Their focus was specifically on activity-dependent genes that are likely to be involved in higher cognitive human brain function.
The team found that the fresh human brain transcriptome had an entirely unique transcriptional pattern compared to a range of neuropsychiatric disease-associated post-mortem transcriptomes. To further explore this difference, the team explored genome-wide transcription multiple times after fresh tissue removal to mimic the post-mortem interval. They observed a rapid reduction in neuronal gene expression. The team also found an increase in expression after the post-mortem interval within inflammatory glial cells. The researchers saw that glial cells grew and sprouted long arm-like appendages for many hours after death.
These findings are important for researchers studying disorders like schizophrenia and Alzheimer’s disease as the team found that the pattern of gene expression in fresh samples did not match that of post-mortem brain gene expression. Understanding these time-dependent changes in gene expression in post-mortem brain samples will be important for interpreting research studies on human brain disorders.
Dr. Jeffrey Loeb, corresponding author, stated:
“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.
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 post-mortem brain studies can be better understood.”
Image credit: By Dr_Microbe – canva.com