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Microglia in the Cerebral Cortex in Autism

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Abstract

We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had significantly more microglia compared to controls (p = 0.02). One such subject had a microglial density in FI within the control range and was also an outlier behaviorally with respect to other subjects with autism. In VC, microglial densities were also significantly greater in individuals with autism versus controls (p = 0.0002). Since we observed increased densities of microglia in two functionally and anatomically disparate cortical areas, we suggest that these immune cells are probably denser throughout cerebral cortex in brains of people with autism.

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Notes

  1. In Table 5 of Lyck et al. (2009) the column headed “total neocortex” refers to the neocortical gray matter only. In their methods Section 2.2.7, “Estimation of Cell Numbers,” they describe their selection of the region of interest, saying, “… followed by delineation the border between white matter and neocortex at 210× magnification (10 × lens) marking the white matter as ‘exclusive region’,” indicating that their cell number estimates were made from a region that excluded white matter. Further, Fig. 2b from this paper indicates that the brain slices were segmented into “frontal neocortex,” “temporal neocortex,” “parietal neocortex,” “occipital neocortex,” and “white matter,” implying that the various neocortex segments do not include white matter. Thus, in Table 5 the column heads “frontal cortex,” “temporal cortex,” etc. presumably refer specifically to the gray matter portions of those regions, and “total neocortex” (which is a sum of the other four columns) also includes only gray matter.

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Acknowledgments

This work was supported by grants from the Simons Foundation (SFARI #137661), the James S. McDonnell Foundation, and by NIH grant MH089406. The brain tissue and related anonymous phenotypic information was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders. We especially thank Dr. Ronald Zielke, Robert Johnson and Melissa Davis for providing the brain tissue and anonymous clinical records; our study would not have been possible without their dedicated service. We thank the anonymous reviewers for their helpful comments and criticisms.

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Tetreault, N.A., Hakeem, A.Y., Jiang, S. et al. Microglia in the Cerebral Cortex in Autism. J Autism Dev Disord 42, 2569–2584 (2012). https://doi.org/10.1007/s10803-012-1513-0

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