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Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice
Pompe disease (PD) is caused by lysosomal glycogen accumulation in tissues, including muscles and the central nervous system (CNS). The intravenous infusion of recombinant human acid alpha-glucosidase (rhGAA) rescues the muscle pathologies in PD but does not treat the CNS because rhGAA does not cros...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677380/ https://www.ncbi.nlm.nih.gov/pubmed/33214573 http://dx.doi.org/10.1038/s41598-020-77193-w |
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author | Lee, Ni-Chung Peng, Wei-Hao Tsai, Li-Kai Lu, Yen-Hsu Wang, Hao-Chun Shih, Yao-Chia Pung, Zeng-Xian Hu, Hsi-Yuan Hwu, Wuh-Liang Tseng, Wen-Yih Isaac Chien, Yin-Hsiu |
author_facet | Lee, Ni-Chung Peng, Wei-Hao Tsai, Li-Kai Lu, Yen-Hsu Wang, Hao-Chun Shih, Yao-Chia Pung, Zeng-Xian Hu, Hsi-Yuan Hwu, Wuh-Liang Tseng, Wen-Yih Isaac Chien, Yin-Hsiu |
author_sort | Lee, Ni-Chung |
collection | PubMed |
description | Pompe disease (PD) is caused by lysosomal glycogen accumulation in tissues, including muscles and the central nervous system (CNS). The intravenous infusion of recombinant human acid alpha-glucosidase (rhGAA) rescues the muscle pathologies in PD but does not treat the CNS because rhGAA does not cross the blood–brain barrier (BBB). To understand the CNS pathologies in PD, control and PD mice were followed and analyzed at 9 and 18 months with brain structural and ultrastructural studies. T2-weighted brain magnetic resonance imaging studies revealed the progressive dilatation of the lateral ventricles and thinning of the corpus callosum in PD mice. Electron microscopy (EM) studies at the genu of the corpus callosum revealed glycogen accumulation, an increase in nerve fiber size variation, a decrease in the g-ratio (axon diameter/total fiber diameter), and myelin sheath decompaction. The morphology of oligodendrocytes was normal. Diffusion tensor imaging (DTI) studies at the corpus callosum revealed an increase in axial diffusivity (AD) and mean diffusivity (MD) more significantly in 9-month-old PD mice. The current study suggests that axon degeneration and axon loss occur in aged PD mice and are probably caused by glycogen accumulation in neurons. A drug crossing the BBB or a treatment for directly targeting the brain might be necessary in PD. |
format | Online Article Text |
id | pubmed-7677380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76773802020-11-23 Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice Lee, Ni-Chung Peng, Wei-Hao Tsai, Li-Kai Lu, Yen-Hsu Wang, Hao-Chun Shih, Yao-Chia Pung, Zeng-Xian Hu, Hsi-Yuan Hwu, Wuh-Liang Tseng, Wen-Yih Isaac Chien, Yin-Hsiu Sci Rep Article Pompe disease (PD) is caused by lysosomal glycogen accumulation in tissues, including muscles and the central nervous system (CNS). The intravenous infusion of recombinant human acid alpha-glucosidase (rhGAA) rescues the muscle pathologies in PD but does not treat the CNS because rhGAA does not cross the blood–brain barrier (BBB). To understand the CNS pathologies in PD, control and PD mice were followed and analyzed at 9 and 18 months with brain structural and ultrastructural studies. T2-weighted brain magnetic resonance imaging studies revealed the progressive dilatation of the lateral ventricles and thinning of the corpus callosum in PD mice. Electron microscopy (EM) studies at the genu of the corpus callosum revealed glycogen accumulation, an increase in nerve fiber size variation, a decrease in the g-ratio (axon diameter/total fiber diameter), and myelin sheath decompaction. The morphology of oligodendrocytes was normal. Diffusion tensor imaging (DTI) studies at the corpus callosum revealed an increase in axial diffusivity (AD) and mean diffusivity (MD) more significantly in 9-month-old PD mice. The current study suggests that axon degeneration and axon loss occur in aged PD mice and are probably caused by glycogen accumulation in neurons. A drug crossing the BBB or a treatment for directly targeting the brain might be necessary in PD. Nature Publishing Group UK 2020-11-19 /pmc/articles/PMC7677380/ /pubmed/33214573 http://dx.doi.org/10.1038/s41598-020-77193-w Text en © The Author(s) 2020 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/. |
spellingShingle | Article Lee, Ni-Chung Peng, Wei-Hao Tsai, Li-Kai Lu, Yen-Hsu Wang, Hao-Chun Shih, Yao-Chia Pung, Zeng-Xian Hu, Hsi-Yuan Hwu, Wuh-Liang Tseng, Wen-Yih Isaac Chien, Yin-Hsiu Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice |
title | Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice |
title_full | Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice |
title_fullStr | Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice |
title_full_unstemmed | Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice |
title_short | Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice |
title_sort | ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in pompe disease mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677380/ https://www.ncbi.nlm.nih.gov/pubmed/33214573 http://dx.doi.org/10.1038/s41598-020-77193-w |
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