Abstract

An ever-increasing body of literature describes compelling evidence that a subset of young children on the autism spectrum show abnormal cerebral growth trajectories. In these cases, normal cerebral size at birth is followed by a period of abnormal growth and starting in late childhood often by regression compared to unaffected controls. Recent work has demonstrated an abnormal increase in the number of neurons of the prefrontal cortex suggesting that cerebral size increase in autism is driven by excess neuronal production. In addition, some affected children display patches of abnormal laminar positioning of cortical projection neurons. As both cortical projection neuron numbers and their correct layering within the developing cortex requires the undisturbed proliferation of neural progenitors, it appears that neural progenitors lie in the center of the autism pathology associated with early brain overgrowth. Consequently, autism spectrum disorders associated with cerebral enlargement should be viewed as birth defects of an early embryonic origin with profound implications for their early diagnosis, preventive strategies, and therapeutic intervention.

Highlights

  • Autism spectrum disorders (ASDs, exchangeably used with autism in this review) comprise a complex of neurodevelopmental behavioral anomalies centered on three core deficits: language impairment, social impairment, and limited interests often accompanied by repetitive actions

  • The most plausible explanation for this unusual cerebral overgrowth appears to be an increase in the proliferation of neural progenitors during embryonic development, which has been convincingly corroborated by animal models

  • Developmental megalencephaly may be a point of confluence for both genetic and environmental factors in ASDs as work on maternal inflammation during pregnancy suggests

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Summary

Prenatal Neurogenesis in Autism Spectrum Disorders

Tibor Kristian, University of Maryland School of Medicine, USA Martin Bienengraeber, Medical College of Wisconsin, USA. An ever-increasing body of literature describes compelling evidence that a subset of young children on the autism spectrum show abnormal cerebral growth trajectories. In these cases, normal cerebral size at birth is followed by a period of abnormal growth and starting in late childhood often by regression compared to unaffected controls. Some affected children display patches of abnormal laminar positioning of cortical projection neurons As both cortical projection neuron numbers and their correct layering within the developing cortex requires the undisturbed proliferation of neural progenitors, it appears that neural progenitors lie in the center of the autism pathology associated with early brain overgrowth.

INTRODUCTION
ALTERED NEUROGENESIS IN ASDs
NEURAL PROGENITORS AND ASDs
Findings
CONCLUSION AND FUTURE STEPS
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