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Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain.

Fabien Dachet1, James B Brown2, Tibor Valyi-Nagy3

  • 1University of Illinois at Chicago, Chicago, IL, 60612, USA. fdachet@uic.edu.

Scientific Reports
|March 24, 2021
PubMed
Summary
This summary is machine-generated.

Postmortem interval significantly alters human brain gene expression, with rapid neuronal gene loss and increased glial gene activity. Understanding these changes is crucial for interpreting studies on brain disorders.

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Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Human brain research often relies on postmortem samples, which may not accurately reflect the in vivo state.
  • Understanding transcriptional changes during the postmortem interval is critical for accurate interpretation of disease-associated gene expression.

Purpose of the Study:

  • To compare transcriptional patterns and histological features between fresh surgical human neocortex and postmortem brain tissue.
  • To investigate genome-wide transcription changes over time after tissue removal to mimic the postmortem interval.
  • To elucidate the dynamic cellular and molecular alterations occurring during the postmortem interval in the human brain.

Main Methods:

  • Genome-wide transcription profiling of fresh human neocortex and postmortem brain tissue.
  • Time-course analysis of gene expression following surgical tissue resection.
  • Histological examination of tissue to correlate with transcriptional changes.

Main Results:

  • Fresh human brain transcriptome shows unique patterns compared to postmortem samples.
  • Rapid reduction in neuronal activity-dependent transcripts within hours of tissue removal.
  • Reciprocal time-dependent increase in astroglial and microglial gene expression over 24 hours.
  • Histological confirmation of neuronal degeneration and glial process outgrowth.

Conclusions:

  • The postmortem interval induces rapid and significant dynamic transcriptional and cellular changes in the human brain.
  • Neuronal gene expression declines rapidly, while glial gene expression increases, affecting sample integrity.
  • Accurate interpretation of human brain disorder research requires consideration of postmortem interval-induced gene expression alterations.