title: Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism.
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.
authors.affiliation: Department of Neuroscience, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0602, USA. jtmorgan61@gmail.com
authors.forename: John T
authors.initials: JT
authors.lastname: Morgan
authors.forename: Gursharan
authors.initials: G
authors.lastname: Chana
authors.forename: Ian
authors.initials: I
authors.lastname: Abramson
authors.forename: Katerina
authors.initials: K
authors.lastname: Semendeferi
authors.forename: Eric
authors.initials: E
authors.lastname: Courchesne
authors.forename: Ian P
authors.initials: IP
authors.lastname: Everall
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000473:pathology*; D001344:Autopsy; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008297:Male; D017628:Microglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D017397:Prefrontal Cortex / Q000473:pathology*; D055815:Young Adult