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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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.
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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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