Dataset Information

Microglial regional heterogeneity and its role in the brain.

ABSTRACT: Microglia have been recently shown to manifest a very interesting phenotypical heterogeneity across different regions in the mammalian central nervous system (CNS). However, the underlying mechanism and functional meaning of this phenomenon are currently unclear. Baseline diversities of adult microglia in their cell number, cellular and subcellular structures, molecular signature as well as relevant functions have been discovered. But recent transcriptomic studies using bulk RNAseq and single-cell RNAseq have produced conflicting results on region-specific signatures of microglia. It is highly speculative whether such spatial heterogeneity contributes to varying sensitivities of individual microglia to the same physiological and pathological signals in different CNS regions, and hence underlie their functional relevance for CNS disease development. This review aims to thoroughly summarize up-to-date knowledge on this specific topic and provide some insights on the potential underlying mechanisms, starting from microgliogenesis. Understanding regional heterogeneity of microglia in the context of their diverse neighboring neurons and other glia may provide an important clue for future development of innovative therapies for neuropsychiatric disorders.

SUBMITTER: Tan YL

PROVIDER: S-EPMC6974435 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Microglial regional heterogeneity and its role in the brain.

Tan Yun-Long YL Yuan Yi Y Tian Li L

Molecular psychiatry 20191126 2

Microglia have been recently shown to manifest a very interesting phenotypical heterogeneity across different regions in the mammalian central nervous system (CNS). However, the underlying mechanism and functional meaning of this phenomenon are currently unclear. Baseline diversities of adult microglia in their cell number, cellular and subcellular structures, molecular signature as well as relevant functions have been discovered. But recent transcriptomic studies using bulk RNAseq and single-ce ...[more]

PMID: 31772305

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Project description:ImportanceSchizophrenia is associated with alterations in mean regional brain volumes. However, it is not known whether the clinical heterogeneity seen in the disorder is reflected at the neurobiological level, for example, in differences in the interindividual variability of these brain volumes relative to control individuals.ObjectiveTo investigate whether patients with first-episode schizophrenia exhibit greater variability of regional brain volumes in addition to mean volume differences.Data sourcesStudies that reported regional brain volumetric measures in patients and controls by using magnetic resonance imaging in the MEDLINE, EMBASE, and PsycINFO databases from inception to October 1, 2016, were examined.Study selectionCase-control studies that reported regional brain volumes in patients with first-episode schizophrenia and healthy controls by using magnetic resonance imaging were selected.Data extraction and synthesisMeans and variances (SDs) were extracted for each measure to calculate effect sizes, which were combined using multivariate meta-analysis.Main outcomes and measuresRelative variability of regional brain volumetric measurements in patients compared with control groups as indexed by the variability ratio (VR) and coefficient of variation ratio (CVR). Hedges g was used to quantify mean differences.ResultsA total of 108 studies that reported measurements from 3901 patients (1272 [32.6%] female) with first-episode schizophrenia and 4040 controls (1613 [39.9%] female) were included in the analyses. Variability of putamen (VR, 1.13; 95% CI, 1.03-1.24; P = .01), temporal lobe (VR, 1.12; 95% CI, 1.04-1.21; P = .004), thalamus (VR, 1.16; 95% CI, 1.07-1.26; P < .001), and third ventricle (VR, 1.43; 95% CI, 1.20-1.71; P < 1 × 10-5) volume was significantly greater in patients, whereas variability of anterior cingulate cortex volume was lower (VR, 0.89; 95% CI, 0.81-0.98; P = .02). These findings were robust to choice of outcome measure. There was no evidence of altered variability of caudate nucleus or frontal lobe volumes. Mean volumes of the lateral (g = 0.40; 95% CI, 0.29-0.51; P < .001) and third ventricles (g = 0.43; 95% CI, 0.26-0.59; P < .001) were greater, whereas mean volumes of the amygdala (g = -0.46; -0.65 to -0.26; P < .001), anterior cingulate cortex (g = -0.26; 95% CI, -0.43 to -0.10; P = .005), frontal lobe (g = -0.31; 95% CI, -0.44 to -0.19; P = .001), hippocampus (g = -0.66; 95% CI, -0.84 to -0.47; P < .001), temporal lobe (g = -0.22; 95% CI, -0.36 to -0.09; P = .001), and thalamus (g = -0.36; 95% CI, -0.57 to -0.15; P = .001) were lower in patients. There was no evidence of altered mean volume of caudate nucleus or putamen.Conclusions and relevanceIn addition to altered mean volume of many brain structures, schizophrenia is associated with significantly greater variability of temporal cortex, thalamus, putamen, and third ventricle volumes, consistent with biological heterogeneity in these regions, but lower variability of anterior cingulate cortex volume. This finding indicates greater homogeneity of anterior cingulate volume and, considered with the significantly lower mean volume of this region, suggests that this is a core region affected by the disorder.

Dataset Information

Microglial regional heterogeneity and its role in the brain.

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Microglial regional heterogeneity and its role in the brain.

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