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A loss of mature microglial markers without immune activation in schizophrenia.

ABSTRACT: Microglia, the immune cells of the brain, are important for neurodevelopment and have been hypothesized to play a role in the pathogenesis of schizophrenia (SCZ). Although previous postmortem studies pointed toward presence of microglial activation, this view has been challenged by more recent hypothesis-driven and hypothesis-free analyses. The aim of the present study is to further understand the observed microglial changes in SCZ. We first performed a detailed meta-analysis on studies that analyzed microglial cell density, microglial morphology, and expression of microglial-specific markers. We then further explored findings from the temporal cortex by performing immunostainings and qPCRs on an additional dataset. A random effect meta-analysis showed that the density of microglial cells was unaltered in SCZ (ES: 0.144 95% CI: 0.102 to 0.390, p = .250), and clear changes in microglial morphology were also absent. The expression of several microglial specific genes, such as CX3CR1, CSF1R, IRF8, OLR1, and TMEM119 was decreased in SCZ (ES: -0.417 95% CI: -0.417 to -0.546, p < .0001), consistent with genome-wide transcriptome meta-analysis results. These results indicate a change in microglial phenotype rather than density, which was validated with the use of TMEM119/Iba1 immunostainings on temporal cortex of a separate cohort. Changes in microglial gene expression were overlapping between SCZ and other psychiatric disorders, but largely opposite from changes reported in Alzheimer's disease. This distinct microglial phenotype provides a crucial molecular hallmark for future research into the role of microglia in SCZ and other psychiatric disorders.

SUBMITTER: Snijders GJLJ

PROVIDER: S-EPMC7986895 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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A loss of mature microglial markers without immune activation in schizophrenia.

Snijders Gijsje J L J GJLJ van Zuiden Welmoed W Sneeboer Marjolein A M MAM Berdenis van Berlekom Amber A van der Geest Astrid T AT Schnieder Tatiana T MacIntyre Donald J DJ Hol Elly M EM Kahn René S RS de Witte Lot D LD

Glia 20210107 5

Microglia, the immune cells of the brain, are important for neurodevelopment and have been hypothesized to play a role in the pathogenesis of schizophrenia (SCZ). Although previous postmortem studies pointed toward presence of microglial activation, this view has been challenged by more recent hypothesis-driven and hypothesis-free analyses. The aim of the present study is to further understand the observed microglial changes in SCZ. We first performed a detailed meta-analysis on studies that ana ...[more]

PMID: 33410555

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A loss of mature microglial markers without immune activation in schizophrenia.

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A loss of mature microglial markers without immune activation in schizophrenia.

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