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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996118305515 |
| _version_ | 1818648967745896448 |
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| author | Carola I. Radulescu Marta Garcia-Miralles Harwin Sidik Costanza Ferrari Bardile Nur Amirah Binte Mohammad Yusof Hae Ung Lee Eliza Xin Pei Ho Collins Wenhan Chu Emma Layton Donovan Low Paola Florez De Sessions Sven Pettersson Florent Ginhoux Mahmoud A. Pouladi |
| author_facet | Carola I. Radulescu Marta Garcia-Miralles Harwin Sidik Costanza Ferrari Bardile Nur Amirah Binte Mohammad Yusof Hae Ung Lee Eliza Xin Pei Ho Collins Wenhan Chu Emma Layton Donovan Low Paola Florez De Sessions Sven Pettersson Florent Ginhoux Mahmoud A. Pouladi |
| author_sort | Carola I. Radulescu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T01:26:51Z |
| format | Article |
| id | doaj.art-57a94a7b970649ec909b982d493a2399 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T01:26:51Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-57a94a7b970649ec909b982d493a23992022-12-21T22:08:40ZengElsevierNeurobiology of Disease1095-953X2019-07-011276575Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington diseaseCarola I. Radulescu0Marta Garcia-Miralles1Harwin Sidik2Costanza Ferrari Bardile3Nur Amirah Binte Mohammad Yusof4Hae Ung Lee5Eliza Xin Pei Ho6Collins Wenhan Chu7Emma Layton8Donovan Low9Paola Florez De Sessions10Sven Pettersson11Florent Ginhoux12Mahmoud A. Pouladi13Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 138648, Singapore; Department of Psychology, The University of Sheffield, S1 2LT, UKTranslational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 138648, SingaporeTranslational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 138648, SingaporeTranslational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 138648, SingaporeTranslational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 138648, SingaporeLee Kong Chian School of Medicine, Nanyang Technological University, 637551, SingaporeGIS Efficient Rapid Microbial Sequencing, Genome Institute of Singapore, A*STAR, 138672, SingaporeGIS Efficient Rapid Microbial Sequencing, Genome Institute of Singapore, A*STAR, 138672, SingaporeGIS Efficient Rapid Microbial Sequencing, Genome Institute of Singapore, A*STAR, 138672, SingaporeSingapore Immunology Network, A*STAR, 138648, SingaporeGIS Efficient Rapid Microbial Sequencing, Genome Institute of Singapore, A*STAR, 138672, SingaporeLee Kong Chian School of Medicine, Nanyang Technological University, 637551, Singapore; Singapore Centre for Environmental Life Sciences Engineering, 60 Nanyang Drive, 637551, SingaporeSingapore Immunology Network, A*STAR, 138648, SingaporeTranslational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 138648, Singapore; Department of Medicine, National University of Singapore, 117597, Singapore; Department of Physiology, National University of Singapore, 117597, Singapore; Corresponding author at: TLGM, A*STAR, 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.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.http://www.sciencedirect.com/science/article/pii/S0969996118305515Huntington diseaseBACHDWhite matterMyelinationOligodendrocytesGerm-free |
| spellingShingle | Carola I. Radulescu Marta Garcia-Miralles Harwin Sidik Costanza Ferrari Bardile Nur Amirah Binte Mohammad Yusof Hae Ung Lee Eliza Xin Pei Ho Collins Wenhan Chu Emma Layton Donovan Low Paola Florez De Sessions Sven Pettersson Florent Ginhoux Mahmoud A. Pouladi Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease Neurobiology of Disease Huntington disease BACHD White matter Myelination Oligodendrocytes Germ-free |
| title | 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_short | 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 |
| topic | Huntington disease BACHD White matter Myelination Oligodendrocytes Germ-free |
| url | http://www.sciencedirect.com/science/article/pii/S0969996118305515 |
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