Factors Affecting Ultrastructural Quality in the Prefrontal Cortex of the Postmortem Human Brain

J Histochem Cytochem. 2019 Mar;67(3):185-202. doi: 10.1369/0022155418819481. Epub 2018 Dec 18.


Electron microscopy (EM) studies of the postmortem human brain provide a level of resolution essential for understanding brain function in both normal and disease states. However, processes associated with death can impair the cellular and organelle ultrastructural preservation required for quantitative EM studies. Although postmortem interval (PMI), the time between death and preservation of tissue, is thought to be the most influential factor of ultrastructural quality, numerous other factors may also influence tissue preservation. The goal of the present study was to assess the effects of pre- and postmortem factors on multiple components of ultrastructure in the postmortem human prefrontal cortex. Tissue samples from 30 subjects were processed using standard EM histochemistry. The primary dependent measure was number of identifiable neuronal profiles, and secondary measures included presence and/or integrity of synapses, mitochondria, and myelinated axonal fibers. Number of identifiable neuronal profiles was most strongly affected by the interaction of PMI and pH, such that short PMIs and neutral pH values predicted the best preservation. Secondary measures were largely unaffected by pre- and postmortem factors. Together, these data indicate that distinct components of the neuropil are differentially affected by PMI and pH in postmortem human brain.

Keywords: G-ratio; acidosis; cause of death; degeneration; gray matter; mitochondria; neuropil; oligodendrocyte; postsynaptic density; psychiatric disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / pathology
  • Case-Control Studies
  • Cause of Death
  • Female
  • Histocytochemistry / methods
  • Histocytochemistry / standards*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Mental Disorders / pathology
  • Middle Aged
  • Mitochondria / ultrastructure
  • Nerve Fibers, Myelinated / ultrastructure*
  • Neurons / ultrastructure*
  • Neuropil / ultrastructure*
  • Postmortem Changes
  • Prefrontal Cortex / anatomy & histology
  • Prefrontal Cortex / pathology
  • Prefrontal Cortex / ultrastructure*
  • Substance-Related Disorders / pathology
  • Synapses / ultrastructure*
  • Time Factors
  • Tissue Preservation / methods