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Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise

1 in 20 live births in the United States is affected by prenatal alcohol exposure annually, creating a major public health crisis. The teratogenic impact of alcohol on physical growth, neurodevelopment, and behavior is extensive, together resulting in clinical disorders which fall under the umbrella...

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Autores principales: Milbocker, Katrina A., LeBlanc, Gillian L., Brengel, Eric K., Hekmatyar, Khan S., Kulkarni, Praveen, Ferris, Craig F., Klintsova, Anna Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226126/
https://www.ncbi.nlm.nih.gov/pubmed/35739222
http://dx.doi.org/10.1038/s41598-022-14752-3
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author Milbocker, Katrina A.
LeBlanc, Gillian L.
Brengel, Eric K.
Hekmatyar, Khan S.
Kulkarni, Praveen
Ferris, Craig F.
Klintsova, Anna Y.
author_facet Milbocker, Katrina A.
LeBlanc, Gillian L.
Brengel, Eric K.
Hekmatyar, Khan S.
Kulkarni, Praveen
Ferris, Craig F.
Klintsova, Anna Y.
author_sort Milbocker, Katrina A.
collection PubMed
description 1 in 20 live births in the United States is affected by prenatal alcohol exposure annually, creating a major public health crisis. The teratogenic impact of alcohol on physical growth, neurodevelopment, and behavior is extensive, together resulting in clinical disorders which fall under the umbrella term of Fetal Alcohol Spectrum Disorders (FASD). FASD-related impairments to executive function and perceptual learning are prevalent among affected youth and are linked to disruptions to corpus callosum growth and myelination in adolescence. Targeted interventions that support neurodevelopment in FASD-affected youth are nonexistent. We evaluated the capacity of an adolescent exercise intervention, a stimulator of myelinogenesis, to upregulate corpus callosum myelination in a rat model of FASD (third trimester-equivalent alcohol exposure). This study employs in vivo diffusion tensor imaging (DTI) scanning to investigate the effects of: (1) neonatal alcohol exposure and (2) an adolescent exercise intervention on corpus callosum myelination in a rodent model of FASD. DTI scans were acquired twice longitudinally (pre- and post-intervention) in male and female rats using a 9.4 Tesla Bruker Biospec scanner to assess alterations to corpus callosum myelination noninvasively. Fractional anisotropy values as well as radial/axial diffusivity values were compared within-animal in a longitudinal study design. Analyses using mixed repeated measures ANOVA’s confirm that neonatal alcohol exposure in a rodent model of FASD delays the trajectory of corpus callosum growth and myelination across adolescence, with a heightened vulnerability in the male brain. Alterations to corpus callosum volume are correlated with reductions to forebrain volume which mediates an indirect relationship between body weight gain and corpus callosum growth. While we did not observe any significant effects of voluntary aerobic exercise on corpus callosum myelination immediately after completion of the 12-day intervention, we did observe a beneficial effect of exercise intervention on corpus callosum volume growth in all rats. In line with clinical findings, we have shown that prenatal alcohol exposure leads to hypomyelination of the corpus callosum in adolescence and that the severity of damage is sexually dimorphic. Further, exercise intervention improves corpus callosum growth in alcohol-exposed and control rats in adolescence.
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spelling pubmed-92261262022-06-25 Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise Milbocker, Katrina A. LeBlanc, Gillian L. Brengel, Eric K. Hekmatyar, Khan S. Kulkarni, Praveen Ferris, Craig F. Klintsova, Anna Y. Sci Rep Article 1 in 20 live births in the United States is affected by prenatal alcohol exposure annually, creating a major public health crisis. The teratogenic impact of alcohol on physical growth, neurodevelopment, and behavior is extensive, together resulting in clinical disorders which fall under the umbrella term of Fetal Alcohol Spectrum Disorders (FASD). FASD-related impairments to executive function and perceptual learning are prevalent among affected youth and are linked to disruptions to corpus callosum growth and myelination in adolescence. Targeted interventions that support neurodevelopment in FASD-affected youth are nonexistent. We evaluated the capacity of an adolescent exercise intervention, a stimulator of myelinogenesis, to upregulate corpus callosum myelination in a rat model of FASD (third trimester-equivalent alcohol exposure). This study employs in vivo diffusion tensor imaging (DTI) scanning to investigate the effects of: (1) neonatal alcohol exposure and (2) an adolescent exercise intervention on corpus callosum myelination in a rodent model of FASD. DTI scans were acquired twice longitudinally (pre- and post-intervention) in male and female rats using a 9.4 Tesla Bruker Biospec scanner to assess alterations to corpus callosum myelination noninvasively. Fractional anisotropy values as well as radial/axial diffusivity values were compared within-animal in a longitudinal study design. Analyses using mixed repeated measures ANOVA’s confirm that neonatal alcohol exposure in a rodent model of FASD delays the trajectory of corpus callosum growth and myelination across adolescence, with a heightened vulnerability in the male brain. Alterations to corpus callosum volume are correlated with reductions to forebrain volume which mediates an indirect relationship between body weight gain and corpus callosum growth. While we did not observe any significant effects of voluntary aerobic exercise on corpus callosum myelination immediately after completion of the 12-day intervention, we did observe a beneficial effect of exercise intervention on corpus callosum volume growth in all rats. In line with clinical findings, we have shown that prenatal alcohol exposure leads to hypomyelination of the corpus callosum in adolescence and that the severity of damage is sexually dimorphic. Further, exercise intervention improves corpus callosum growth in alcohol-exposed and control rats in adolescence. Nature Publishing Group UK 2022-06-23 /pmc/articles/PMC9226126/ /pubmed/35739222 http://dx.doi.org/10.1038/s41598-022-14752-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Milbocker, Katrina A.
LeBlanc, Gillian L.
Brengel, Eric K.
Hekmatyar, Khan S.
Kulkarni, Praveen
Ferris, Craig F.
Klintsova, Anna Y.
Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise
title Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise
title_full Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise
title_fullStr Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise
title_full_unstemmed Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise
title_short Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise
title_sort reduced and delayed myelination and volume of corpus callosum in an animal model of fetal alcohol spectrum disorders partially benefit from voluntary exercise
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226126/
https://www.ncbi.nlm.nih.gov/pubmed/35739222
http://dx.doi.org/10.1038/s41598-022-14752-3
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