Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects
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 anat...
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doaj-c641683615624921bd1d22b4d4c1b68d2020-11-25T01:15:03ZengBMCActa Neuropathologica Communications2051-59602018-12-016111410.1186/s40478-018-0645-7Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjectsJarek Wegiel0Wojciech Kaczmarski1Michael Flory2Veronica Martinez-Cerdeno3Thomas Wisniewski4Krzysztof Nowicki5Izabela Kuchna6Jerzy Wegiel7Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental DisabilitiesDepartment of Developmental Neurobiology, New York State Institute for Basic Research in Developmental DisabilitiesResearch Design and Analysis Services, New York State Institute for Basic Research in Developmental DisabilitiesPathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, MIND Institute, University of CaliforniaDepartments of Neurology, Pathology and Psychiatry, NYU Langone Medical CenterDepartment of Developmental Neurobiology, New York State Institute for Basic Research in Developmental DisabilitiesDepartment of Developmental Neurobiology, New York State Institute for Basic Research in Developmental DisabilitiesDepartment of Developmental Neurobiology, New York State Institute for Basic Research in Developmental DisabilitiesAbstract 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.http://link.springer.com/article/10.1186/s40478-018-0645-7AutismNeuropathologyCorpus callosumAxonElectron microscopyMorphometry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jarek Wegiel Wojciech Kaczmarski Michael Flory Veronica Martinez-Cerdeno Thomas Wisniewski Krzysztof Nowicki Izabela Kuchna Jerzy Wegiel |
spellingShingle |
Jarek Wegiel Wojciech Kaczmarski Michael Flory Veronica Martinez-Cerdeno Thomas Wisniewski Krzysztof Nowicki Izabela Kuchna Jerzy Wegiel Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects Acta Neuropathologica Communications Autism Neuropathology Corpus callosum Axon Electron microscopy Morphometry |
author_facet |
Jarek Wegiel Wojciech Kaczmarski Michael Flory Veronica Martinez-Cerdeno Thomas Wisniewski Krzysztof Nowicki Izabela Kuchna Jerzy Wegiel |
author_sort |
Jarek Wegiel |
title |
Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects |
title_short |
Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects |
title_full |
Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects |
title_fullStr |
Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects |
title_full_unstemmed |
Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects |
title_sort |
deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2018-12-01 |
description |
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. |
topic |
Autism Neuropathology Corpus callosum Axon Electron microscopy Morphometry |
url |
http://link.springer.com/article/10.1186/s40478-018-0645-7 |
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