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Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia

Natalya A Uranova1, Olga V Vikhreva2, Valentina I Rakhmanova2

  • 1Mental Health Research Centre, Zagorodnoe shosse 2, 117152, Moscow, Russia. uranovan@mail.ru.

NPJ Schizophrenia
|December 15, 2018
PubMed

Insights

Microglial activation in schizophrenia (SCZ) was investigated. While oligodendrocytes showed dystrophic changes in SCZ brains, particularly in those with positive symptoms, these alterations were not quantitatively linked to microglial activation in white matter.

Area of Science:

  • Neuroscience
  • Pathology
  • Cell Biology

Background:

  • Microglial activation is implicated in schizophrenia pathophysiology.
  • Previous studies reported oligodendrocyte dystrophy in schizophrenia prefrontal white matter.

Purpose of the Study:

  • To investigate the association between oligodendrocyte dystrophy and microglial activation in acute schizophrenia.
  • To examine white matter changes in the prefrontal cortex (BA10) in schizophrenia patients.

Main Methods:

  • Electron microscopy was used to analyze oligodendrocyte organelles (mitochondria, endoplasmic reticulum vacuoles, lipofuscin).
  • Oligodendrocytes adjacent to microglia, myelin, neurons, and capillaries were compared in post-mortem brain tissue from 21 schizophrenia cases and 20 controls.
  • Quantitative analysis of cell density, size, volume fraction, and organelle number was performed.

Main Results:

  • Oligodendrocyte cell density was unchanged in schizophrenia.
  • Decreased mitochondria and increased endoplasmic reticulum vacuoles and lipofuscin were observed in oligodendrocytes adjacent to microglia or myelin in schizophrenia patients, especially those with positive symptoms.
  • Increased lipofuscin was also noted in peri-capillary oligodendrocytes.
  • No quantitative evidence supported a direct association between oligodendrocyte dystrophy and microglial activation in schizophrenia white matter.

Conclusions:

  • Schizophrenia is associated with specific ultrastructural changes in oligodendrocytes, including mitochondrial dysfunction and accumulation of lipofuscin.
  • These oligodendrocyte alterations, particularly in the acute state and positive symptom group, occur independently of direct microglial activation.
  • Further research is needed to elucidate the precise mechanisms driving oligodendrocyte pathology in schizophrenia.

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