TY - JOUR
T1 - Reprint of
T2 - Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease
AU - Radulescu, Carola I.
AU - Garcia-Miralles, Marta
AU - Sidik, Harwin
AU - Bardile, Costanza Ferrari
AU - Yusof, Nur Amirah Binte Mohammad
AU - Lee, Hae Ung
AU - Ho, Eliza Xin Pei
AU - Chu, Collins Wenhan
AU - Layton, Emma
AU - Low, Donovan
AU - De Sessions, Paola Florez
AU - Pettersson, Sven
AU - Ginhoux, Florent
AU - Pouladi, Mahmoud A.
N1 - Publisher Copyright:
© 2020
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - BACHD
KW - Germ-free
KW - Huntington disease
KW - Microbiome
KW - Microbiota
KW - Myelination
KW - Oligodendrocytes
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85077916700&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2020.104744
DO - 10.1016/j.nbd.2020.104744
M3 - Article
C2 - 31931139
AN - SCOPUS:85077916700
SN - 0969-9961
VL - 135
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 104744
ER -