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Axonal transport is a fundamental neuronal cell function, which supplies neuron materials and conveys information. Thus, any increase or decrease in axonal transport expresses the state of neurons, and impairment of axonal transport is a cause of neuronal degeneration. Excessive reactive oxygen species (ROS) have been implicated in damage to neurons, therefore oxidative stress is known to be a major cause of neurodegenerative diseases. Cu/Zn superoxide dismutase (SOD1) is an enzyme, which protects cells against ROS. In this study, we investigated the effects of the SOD1 inhibitor diethyldithiocarbamate (DDC) on axonal transport in cultured dorsal root ganglion neurons. Adult male C57BL/6 mice (n=5) were euthanized by intraperitoneal injection of pentobarbital sodium (60 mg/kg of body weight), and dorsal root ganglia were removed. Cells were enzymatically and mechanically isolated and cultured for 48 h in Ham's F-12 medium containing 10% fetal bovine serum at 37°C under humidified condition in 5% CO2. Movement of organelles in neurites was observed in real-time by using videoenhanced microscopy, and the number of organelles transported in anterograde and retrograde directions was counted manually before and during the addition of DDC (the number of experiments=48). DDC significantly reduced the number of transported organelles in a time-dependent manner, compared with PSS. The percentage of transported organelles after 40-min treatment with DDC was 50% of the baseline (before application with DDC, in the control PSS medium) at 100 nM, 43% at 1 µM, 25% at 10 µM, 9% at 100 µM. We further examined whether the anti-oxidant α-tocopherol can prevent DDC-induced inhibition of axonal transport. The inhibitory effects of DDC on axonal transport was partially blocked by pretreatment with α-tocopherol, the value after 40-min treatment with DDC at 100 nM-100 µM was significantly higher than administration of DDC alone. These results suggested that endogenous oxidative stress increased with DDC treatment and that it inhibited axonal transport. The DDC-induced inhibition of axonal transport was blocked by α-tocopherol. Based on these things, α-tocopherol might be of help in rescuing impairment of axonal transport in response to oxidative stress. [ABSTRACT FROM AUTHOR]