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Acta Neuropathol Commun. 2018 Dec 19;6(1):143. doi: 10.1186/s40478-018-0645-7.

Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects.

Author information

1
Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA. Jarek.Wegiel@opwdd.ny.gov.
2
Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA.
3
Research Design and Analysis Services, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 10314, USA.
4
Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, MIND Institute, University of California, Davis, CA, USA.
5
Departments of Neurology, Pathology and Psychiatry, NYU Langone Medical Center, New York, NY, USA.

Abstract

INTRODUCTION:

In autism spectrum disorder, lack of coherence and of complex information processing, and narrowly focused interests and repetitive behaviors are considered a sign of long-range underconnectivity and short-range overconnectivity. The goal of this morphometric study of five anatomically and functionally different segments of the corpus callosum (CC) was to establish patterns of differences between long-range interhemispheric connections in nine neurotypical and nine autistic subjects.

RESULTS:

Electron microscopy revealed a significant reduction in average axon diameter and axon cross-sectional area in autistic subjects, and reduction in CC segment-specific diversification of connections of functionally different cortical regions. The study shows an increase in the percentage of small diameter axons (< 0.651 μm) and a decrease in the percentage of axons with large diameter (> 1.051 μm). The total number of small-diameter axons is reduced in segment I and III by 43% on average. The number of medium- and large-diameter axons is reduced in all five CC segments by an average of 49 and 72%, respectively.

CONCLUSIONS:

The detected pattern of pathology suggests a failure of mechanisms controlling guidance of axons during development leading to axonal deficit, and failure of mechanisms controlling axon structure. A reduction in axon diameter may affect the velocity and volume of signal transmission, and distort functional specialization of CC segments. Significant deficits in axon number and reduction in axon size in all five CC segments appear to be substantial components of brain connectome integrity distortion which may contribute to the autism phenotype.

KEYWORDS:

Autism; Axon; Corpus callosum; Electron microscopy; Morphometry; Neuropathology

PMID:
30567587
PMCID:
PMC6299595
DOI:
10.1186/s40478-018-0645-7
[Indexed for MEDLINE]
Free PMC Article

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