Background The contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington Disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented.

Aim Here we sought to investigate spinal cord pathology in a mouse model of HD, and in particular WM and myelination abnormalities.

Method To determine whether GM and WM regions are atrophied in the spinal cord of 12 months old BACHD mice, we measured the area of GM and WM in the spinal cord by histological assessment. Electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord, where g-ratio of myelinated axons was used as a measure of myelin thickness. To investigate the impact of inactivation of mutant huntingtin (mHTT) in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre (BN) mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells (OPC).

Results We show that spinal GM and WM areas are significantly atrophied in BACHD mice compared to wild-type (WT) controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, as observed in BACHD 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.

Conclusions Overall, our findings firstly demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord, and secondly, they suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.