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

Author:

Gober Ryan1ORCID,Dallmeier Julian1ORCID,Davis David12ORCID,Brzostowicki Daniel1,de Rivero Vaccari Juan Pablo3ORCID,Cyr Brianna3ORCID,Barreda Ayled1ORCID,Sun Xiaoyan12ORCID,Gultekin Sakir Humayun124ORCID,Garamszegi Susanna12ORCID,Scott William15ORCID,Vontell Regina12ORCID

Affiliation:

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

2. Department of Neurology, University of Miami Miller School of Medicine , Miami, FL, United States

3. Department of Neurological Surgery and The Miami Project to Cure Paralysis, University of Miami , Miami, FL, United States

4. Department of Pathology, University of Miami Miller School of Medicine , Miami, FL, United States

5. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL, United States

Abstract

Abstract Schizophrenia (SCZ) is a complex psychiatric disorder that involves an inflammatory response thought to be characterized by microglial activation. The inflammasome complex may play critical roles in the pathomechanism of neuroinflammation but how this relates to SCZ remains unclear. In this study, we performed an immunohistochemical (IHC) analysis to compare the expression of inflammasome proteins in brain tissue from donors with SCZ (n = 16) and non-psychiatric donors (NP; n = 13) isolated from the superior frontal cortex (SFC), superior temporal cortex, and anterior cingulate cortex brain regions. To assess changes in the cell populations that express key inflammasome proteins, we performed IHC analyses of apoptosis-associated speck-like protein containing a CARD (ASC), nod-like receptor protein 3 (NLRP3), and interleukin (IL)-18 to determine if these proteins are expressed in microglia, astrocytes, oligodendrocytes, or neurons. Inflammasome proteins were expressed mainly in microglia from SCZ and NP brains. Increased numbers of microglia were present in the SFC of SCZ brains and exhibited higher inflammasome protein expression of ASC, NLRP3, and IL-18 compared to NPs. These findings suggest that increased inflammasome signaling may contribute to the pathology underlying SCZ.

Funder

Gwendolyn Lawliss Trust

Kurt and Ingrid Dahrén Foundation

NIH

Publisher

Oxford University Press (OUP)

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