S100B is a calcium-binding protein that, in the nervous system, is mainly concentrated in glial cells. Although its biological role is still unclear, the protein is hypothesized, at high concentrations, to act in the pathogenesis of neurodegenerative processes, possibly through oxidative stress mechanisms. To investigate this hypothesis we studied the spinal cord of wobbler mice, an animal model of motor neuron degeneration. Using immunocytochemistry, we detected an overexpression of S100B in astrocytes of the cervical spinal cord of these animals. We also confirmed this finding by reverse transcriptase polymerase chain reaction. In the same spinal cord regions, scattered neurons appeared to be immunostained for 4-hydroxynonenal-modified proteins, an indicator of lipid peroxidation. This finding constitutes a sign of oxidative stress-induced neurodegeneration.