Alpha motoneurone input changes in dystrophic MDX mice after sciatic nerve transection

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy. At present, a lot is known about the muscular degeneration in DMD, but few studies have focused on the effects on the central nervous system. In this sense, retrograde changes in the microenvironment around motor neurones in the spinal cord may contribute to the pathogenesis of the dystrophinopathies.

The aim of this study was to investigate synaptic alterations and glial reactivity in the microenvironment close to spinal motor neurones in a DMD animal model.

Six-week-old male MDX mice were subjected to left sciatic nerve transection. The axotomy was performed after the muscular degeneration/regeneration cycles previously described in such animal models. C57BL/10 mice were used as the control. Seven days after surgery, the animals were sacrificed and the lumbar spinal cords processed for immunohistochemistry using antibodies to the major histocompatibility complex of class I (MHC I), synaptophysin, IBA-1 and glial fibrillary acidic protein (GFAP).

MHC I expression increased in both strains after axotomy. Nevertheless, the MDX mice displayed significantly lower MHC I up-regulation. With respect to GFAP expression, the MDX mice showed greater astrogliosis as compared with C57BL/10 mice. The MDX mice displayed a significant decrease in synaptophysin expression. Indeed, the ultrastructural quantitative analysis showed more intense synaptic detachment in MDX mice, indicating a reduction in synaptic activity before and after axotomy.

The reduction in active inputs and increased gliosis in MDX mice may be associated with the muscle degeneration/regeneration cycles that occur postnatally, and could contribute to the seriousness of the disease.