Increased inflammasome protein expression identified in microglia from postmortem brains with schizophrenia

Ryan Gober1, Julian Dallmeier1, David Davis1,2

  • 1Brain Endowment Bank, University of Miami Miller School of Medicine, Miami, FL, United States.

Insights

Neuroinflammation in schizophrenia (SCZ) involves microglial activation and inflammasome signaling. This study found increased inflammasome proteins in microglia within the superior frontal cortex of SCZ brains, suggesting a role in SCZ pathology.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Immunology

Background:

  • Schizophrenia (SCZ) is a complex psychiatric disorder linked to neuroinflammation, particularly microglial activation.
  • The inflammasome complex's role in SCZ pathogenesis and neuroinflammation is not fully understood.

Purpose of the Study:

  • To investigate the expression of key inflammasome proteins (ASC, NLRP3, IL-18) in the brains of individuals with SCZ compared to non-psychiatric controls.
  • To determine the specific cell types (microglia, astrocytes, oligodendrocytes, neurons) expressing these inflammasome proteins in SCZ.

Main Methods:

  • Immunohistochemical (IHC) analysis was performed on brain tissue from SCZ (n=16) and non-psychiatric (NP; n=13) donors.
  • IHC assessed the expression of apoptosis-associated speck-like protein containing a CARD (ASC), nod-like receptor protein 3 (NLRP3), and interleukin (IL)-18.
  • Expression levels were analyzed in the superior frontal cortex (SFC), superior temporal cortex, and anterior cingulate cortex.

Main Results:

  • Inflammasome proteins were primarily detected in microglia in both SCZ and NP brains.
  • SCZ brains showed increased microglial numbers in the SFC compared to NP brains.
  • Higher expression of ASC, NLRP3, and IL-18 was observed in microglia from the SFC of SCZ brains relative to NP controls.

Conclusions:

  • Increased inflammasome protein expression in microglia within the superior frontal cortex is associated with schizophrenia.
  • These findings suggest that heightened inflammasome signaling in microglia may contribute to the neuroinflammatory pathology of SCZ.