Abnormal microglial–neuronal spatial organization in the dorsolateral prefrontal cortex in autism

• Published in: Brain research Vol. 1456; pp. 72 - 81
• Main Authors: Morgan, John T., Chana, Gursharan, Abramson, Ian, Semendeferi, Katerina, Courchesne, Eric, Everall, Ian P.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.05.2012; Elsevier
• Subjects: Adolescent; Adult; Age; Autism; Autistic Disorder; Autistic Disorder - pathology; Autopsy; Biological and medical sciences; Brain; Child; Child clinical studies; Child, Preschool; cortex; Cortex (prefrontal); Developmental disorders; Humans; Infantile autism; Male; Medical sciences; Microglia; Microglia - pathology; neuroglia; Neurology; Neuron; Neurons; Neurons - pathology; pathology; Postmortem; Prefrontal Cortex; Prefrontal Cortex - pathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Spatial organization; Young Adult; Autism; Neuron; Postmortem; Microglia; Spatial organization; Dorsolateral prefrontal cortex; Human; Neuroglia; Developmental disorder
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2012.03.036

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 25μm, as well as 75 and 100μm. 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. ► We examine microglia–neuron interaction and organization in autism. ► Increased presence of microglia near neurons is observed in autism. ► Microglial process encirclement of neuronal somas is apparent in autism. ► Neuronal organization is abnormal in adults with autism. ► Microglial organization is normal in autism, but degrades in all older subjects.