Abnormal Spinal Cord Myelination due to Oligodendrocyte Dysfunction in a Model of Huntington's Disease.
Huntington’s disease
myelin sheath
oligodendroglia
spinal cord
white matter
Journal
Journal of Huntington's disease
ISSN: 1879-6400
Titre abrégé: J Huntingtons Dis
Pays: Netherlands
ID NLM: 101589965
Informations de publication
Date de publication:
2021
2021
Historique:
pubmed:
10
8
2021
medline:
14
1
2022
entrez:
9
8
2021
Statut:
ppublish
Résumé
The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington's disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented. We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits. Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells. We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord. Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.
Sections du résumé
BACKGROUND
The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington's disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented.
OBJECTIVE
We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits.
METHODS
Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells.
RESULTS
We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord.
CONCLUSION
Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.
Identifiants
pubmed: 34366364
pii: JHD210495
doi: 10.3233/JHD-210495
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM