Rotenone Delays Axon Degeneration

Axon degeneration is a common pathological feature of many neurodegenerative diseases, which usually occurs before the cell body apoptosis for injury or chronic inflammation. The designed strategy to delay neuronal cell apoptosis is too late to be efficient to cure these diseases at clinical treatment. To focus on delaying axonal degeneration directly is another useful to deal with this problem. The cultured superior cervical ganglia (SCG) neuron induced to "Wallerian degeneration" is the simplest model to invistigate axon degeneration. In this study, used transected axons, termed "Wallerian degeneration", we find that rotenone delays the primary cultured SCGs neuron Wallerian's degeneration by drugs screen. Immuno-histochemistry and Western blotting assay show that proper concentration of rotenone to delay axon degeneration is 5.0μM, and it is obviously to find its protection in 8-12 hours after axon severed. Our result indicates that compared with other inhibitors of complex I, only rotenone can reduce axon degeneration; ATP Assay shows that rotenone can obviously suspend the decrease of ATP level in axon at 8-12 hours after being cut, which is consistent with the result of western blotting and immuno-histochemistry assay. After severed from the cell body, the ATP in the axon increases a little (in 4 hours after being treated) instead of decreasing rapidly, which suggests that axonomy as a stress induces the acute response. Proteasome activity analysis shows that rotenone can reduce proteasome activity the similar to MG132, a specific inhibitor of proteasome. Perhaps rotenonedelays Wallerian's degeneration partially through inhibiting proteasome activity.