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Brain Res. 2012 May 25;1456:72-81. doi: 10.1016/j.brainres.2012.03.036. Epub 2012 Mar 23.

Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism.

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  • 1Department of Neuroscience, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0602, USA. jtmorgan61@gmail.com

Abstract

Microglial activation and alterations in neuron number have been reported in autism. However, it is unknown whether microglial activation in the disorder includes a neuron-directed microglial response that might reflect neuronal dysfunction, or instead indicates a non-directed, pro-activation brain environment. To address this question, we examined microglial and neuronal organization in the dorsolateral prefrontal cortex, a region of pronounced early brain overgrowth in autism, via spatial pattern analysis of 13 male postmortem autism subjects and 9 controls. We report that microglia are more frequently present near neurons in the autism cases at a distance interval of 25 μm, as well as 75 and 100 μm. Many interactions are observed between near-distance microglia and neurons that appear to involve encirclement of the neurons by microglial processes. Analysis of a young subject subgroup preliminarily suggests that this alteration may be present from an early age in autism. We additionally observed that neuron-neuron clustering, although normal in cases with autism as a whole, increases with advancing age in autism, suggesting a gradual loss of normal neuronal organization in the disorder. Microglia-microglia organization is normal in autism at all ages, indicating that aberrantly close microglia-neuron association in the disorder is not a result of altered microglial distribution. Our findings confirm that at least some microglial activation in the dorsolateral prefrontal cortex in autism is associated with a neuron-specific reaction, and suggest that neuronal organization may degrade later in life in the disorder.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID:
22516109
[PubMed - indexed for MEDLINE]
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