Amphiregulin acts as an autocrine survival factor for adult sensory neurons.

We studied the effect of amphiregulin on axonal outgrowth and survival in sensory neurons in organ cultured and dissociated mouse dorsal root ganglia (DRG). Amphiregulin at 20 ng/ml stimulated axonal outgrowth in both preparations. The EGF receptor inhibitor AG1478 inhibited outgrowth at 10 microM but not at 1 microM, where it abolished the stimulatory effects of amphiregulin. Fluoro-Jade staining and neuronal counting showed that more neurons survived in culture in the presence of amphiregulin while AG1478 at 10 microM but not 1 microM increased cell death. Small and medium sized neurons were immunopositive for both amphiregulin and the EGF receptor. Taken together these results suggest that amphiregulin can act as an autocrine survival factor for sensory neurons and stimulate axonal outgrowth through the EGF receptor.