Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease

Structural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate th...

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Main Authors: Radulescu, Carola I., Garcia-Miralles, Marta, Sidik, Harwin, Bardile, Costanza Ferrari, Nur Amirah Mohammad Yusof, Lee, Hae Ung, Ho, Eliza Xin Pei, Chu, Collins Wenhan, Layton, Emma, Low, Donovan, De Sessions, Paola Florez, Pettersson, Sven, Ginhoux, Florent, Pouladi, Mahmoud A.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/148697
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1486972021-05-08T20:11:56Z Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease Radulescu, Carola I. Garcia-Miralles, Marta Sidik, Harwin Bardile, Costanza Ferrari Nur Amirah Mohammad Yusof Lee, Hae Ung Ho, Eliza Xin Pei Chu, Collins Wenhan Layton, Emma Low, Donovan De Sessions, Paola Florez Pettersson, Sven Ginhoux, Florent Pouladi, Mahmoud A. Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) Science::Medicine Huntington Disease White Matter Structural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University Published version M.A.P. was supported by funds from theAgency for Science Technology and Research and the NationalUniversity of Singapore. S.P. was supported by funds from LKC Schoolof Medicine and SCELSE. 2021-05-05T01:48:26Z 2021-05-05T01:48:26Z 2019 Journal Article Radulescu, C. I., Garcia-Miralles, M., Sidik, H., Bardile, C. F., Nur Amirah Mohammad Yusof, Lee, H. U., Ho, E. X. P., Chu, C. W., Layton, E., Low, D., De Sessions, P. F., Pettersson, S., Ginhoux, F. & Pouladi, M. A. (2019). Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease. Neurobiology of Disease, 127, 65-75. https://dx.doi.org/10.1016/j.nbd.2019.02.011 0969-9961 https://hdl.handle.net/10356/148697 10.1016/j.nbd.2019.02.011 30802499 2-s2.0-85062148030 127 65 75 en Neurobiology of Disease © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Huntington Disease
White Matter
spellingShingle Science::Medicine
Huntington Disease
White Matter
Radulescu, Carola I.
Garcia-Miralles, Marta
Sidik, Harwin
Bardile, Costanza Ferrari
Nur Amirah Mohammad Yusof
Lee, Hae Ung
Ho, Eliza Xin Pei
Chu, Collins Wenhan
Layton, Emma
Low, Donovan
De Sessions, Paola Florez
Pettersson, Sven
Ginhoux, Florent
Pouladi, Mahmoud A.
Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
description Structural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Radulescu, Carola I.
Garcia-Miralles, Marta
Sidik, Harwin
Bardile, Costanza Ferrari
Nur Amirah Mohammad Yusof
Lee, Hae Ung
Ho, Eliza Xin Pei
Chu, Collins Wenhan
Layton, Emma
Low, Donovan
De Sessions, Paola Florez
Pettersson, Sven
Ginhoux, Florent
Pouladi, Mahmoud A.
format Article
author Radulescu, Carola I.
Garcia-Miralles, Marta
Sidik, Harwin
Bardile, Costanza Ferrari
Nur Amirah Mohammad Yusof
Lee, Hae Ung
Ho, Eliza Xin Pei
Chu, Collins Wenhan
Layton, Emma
Low, Donovan
De Sessions, Paola Florez
Pettersson, Sven
Ginhoux, Florent
Pouladi, Mahmoud A.
author_sort Radulescu, Carola I.
title Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
title_short Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
title_full Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
title_fullStr Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
title_full_unstemmed Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
title_sort manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of huntington disease
publishDate 2021
url https://hdl.handle.net/10356/148697
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