Neuronal and glial cell number is altered in a cortical layer-specific manner in autism

Autism spectrum disorder is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors. Changes in the number of specific cell types in the cerebral cortex could produce a dramatic alteration in the regulation of cortical circuits, and thus an alteration of behavior. We investigated whether there are layer-specific changes in the number of neurons, astrocytes, and oligodendrocytes in the prefrontal cortex in postmortem human brains from autism spectrum disorder subjects. We quantified the number of specific cell types in the prefrontal cortex (Brodmann areas 9, 46, and 47) of 10 cases with autism spectrum disorder and 10 age-matched control cases. We found that the number of neurons was increased and the number of astrocytes was decreased in layer II of all three prefrontal areas. Area BA47 was most widely affected presenting with an increased number of neurons and a decreased number of astrocytes in layer II and deeper layers of the cortex. Among other possibilities, the alterations in neuron and glial cell number we report here are consistent with a failure of radial glial cells to shift daughter cell production from neurons to astrocytes during prenatal cortical development in autism spectrum disorder. The data provided here are key anatomical findings that shed light on autism spectrum disorder pathogenesis. Lay abstract The cerebral cortex affected with autism spectrum disorder presents changes in the number of neurons and glia cells, possibly leading to a dysregulation of brain circuits and affecting behavior. However, little is known about cell number alteration in specific layers of the cortex in autism spectrum disorder. We found an increase in the number of neurons and a decrease in the number of astrocytes in specific layers of the prefrontal cortex in postmortem human brains from autism spectrum disorder cases. We hypothesize that this may be due to a failure in neural stem cells to shift differentiation from neurons to glial cells during prenatal brain development. These data provide key anatomical findings that contribute to the bases of autism spectrum disorder pathogenesis.