Inhibition of superoxide dismutase selectively suppresses growth of rat spinal motor neurons: comparison with phosphorylated neurofilament-containing spinal neurons.

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. The reason why only motor neurons are targeted is unknown. Since ALS has been linked to mutations in Cu/Zn superoxide dismutase (SOD1), oxidative stress is regarded as a major cause of ALS. We hypothesized that motor neurons are more susceptible to oxidative stress than other neurons. To test our hypothesis, we investigated differences in neurite growth between motor and non-motor neurons under SOD1 inhibition. Spinal motor neurons were identified by immunocytochemistry using anti-non-phosphorylated neurofilament (NF) antibody (SMI-32). Other neurons immunoreactive to an antibody against phosphorylated NF (SMI-31) were used as a control. Cultured rat spinal neurons were treated with the SOD1 inhibitor diethyldithiocarbamate (DDC). SMI-32-immunoreactive neurons were more sensitive to the growth inhibitory effects of DDC than SMI-31-immunoreactive neurons. Such inhibition was blocked by the antioxidants, L-ascorbic acid, L-histidine, astaxanthin, α-tocopherol, and β-carotene. The results suggested that spinal motor neurons are more vulnerable to oxidative stress than other neurons, which may explain in part the selective degeneration of motor neurons in ALS.