Neurobiology of Disease (Feb 2020)

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

  • 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

Journal volume & issue
Vol. 135
p. 104744

Abstract

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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.

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