Open AccessMicroglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions
Author(s) -
Gober Ryan,
Ardalan Maryam,
Shiadeh Seyedeh Marziyeh Jabbari,
Duque Linda,
Garamszegi Susanna P.,
Ascona Maureen,
Barreda Ayled,
Sun Xiaoyan,
Mallard Carina,
Vontell Regina T.
Publication year - 2022
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.13003
Subject(s) - microglia , corpus callosum , neuroscience , white matter , pathology , biology , medicine , magnetic resonance imaging , inflammation , radiology
Schizophrenia (SCZ) is a psychiatric disorder that can include symptoms of disorganized speech and thoughts with uncertain underlying mechanisms possibly linked to over‐activated microglia. In this study, we used brain samples from sixteen donors with SCZ and thirteen control donors to assess the differential activation of microglia by quantifying density and 3D reconstruction of microglia stained with ionized calcium‐binding adaptor molecule‐1 (Iba1). Our samples consisted of sections from the frontal, temporal, and cingulate cortical gray matter, subcortical white matter regions (SCWM), and included the anterior corpus callosum. In the first series of studies, we performed a density analysis followed by a spatial analysis to ascertain the microglial density, distribution, and soma size in SCZ brains. Second, we performed a series of morphological quantification techniques to investigate the arborization patterns of the microglia in SCZ. The results demonstrated an increase in microglia density in the cortical gray matter regions in SCZ cases, while in the SCWM, there was a significant increase in microglia density in the frontal and temporal, but not in the other brain regions of interest (ROIs). Spatial analysis using the “nearest neighbor” demonstrated that there was no effect in “clustering”, but there were shorter distances between microglia seen in the SCZ cases. The morphological measures showed that there was a region‐dependent increase in the microglia soma size in the SCZ cases while the Sholl analysis revealed a significant decrease in the microglia arborization in the SCZ cases across all the ROI’s studied. An in‐depth 3D reconstruction of microglia in Brodmann area 9 cortical region found that there was a significant association between age and reduced microglial arborization in the SCZ cases. This region‐dependent age association can help determine whether longitudinal changes in microglial activation across age are brain region‐dependent, which may point to potential therapeutic targets.