Morphological changes and altered expression of antioxidant proteins in a heterozygous dynein mutant; a mouse model of spinal muscular atrophy.

OBJECTIVE

There is increased evidence that oxidative stress is involved in exacerbations of neurodegenerative diseases and spinal muscular atrophies.

METHODS

We examined changes in morphology and expression of antioxidant proteins and peroxiredoxins in motor neurons of lumbar spinal cord, dorsal root ganglion sensory neurons, macroglial cells and quadriceps muscles of newborn heterozygous Loa/+ mice ("legs at odd angles"), a mouse model for early onset of the spinal muscular atrophy with lower extremity predominance (SMA-LED).

RESULTS

Our data indicate that newborn Loa-mice develop: neuroinflammation of the sensory and motor neurons; muscular inflammation with atrophic and denervated myofibers; increased expression of neuronal mitochondrial peroxiredoxins (Prxs) 3, 5 and cytoplasmic Prx 6 in motor and sensory neurons, myofibers, fibroblasts of perimysium and chondrocytes of cartilage; and decreased expression of Prx 6 by glial cells and in extracellular space surrounding motor neurons.

CONCLUSION

The decrease in expression of Prx 6 by glial cells and extracellular Prx 6 secretion in early stages of the pathological conditions is consistent with the hypothesis that chronic oxidative stress may lead to neurodegeneration of motor neurons and exacerbation of the pathology.