PTEN/SOCS3 Co-deletion in Dorsal Root Ganglion Neurons for Peripheral Nerve Regeneration

There are approximately 2 million peripheral nerve injuries as a result of trauma each year in the United States. The peripheral nervous system has some capacity for regeneration after injury, but full functional recovery is rare. Recent studies have shown that conditional deletion of two key signaling inhibitors—phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling-3 (SOCS3)—leads to regeneration of injured axons in the optic nerve and the corticospinal tract; however, PTEN and PTEN/SOCS3 co-deletion within the dorsal root ganglia (DRG)-the location of peripheral sensory neurons-has not been previously investigated. Therefore, we tested the hypothesis that PTEN and/or PTEN/SOCS3 co-deletion in the DRG will enhance regeneration of sensory axons following a sciatic nerve crush. Immunofluorescent staining of DRG sections determined the expression profile of PTEN and the active form of ribosomal protein S6, an indicator of PI3K signaling. Western blot analysis showed that the PI3K and Jack/Stat pathways were activated for a relatively brief period after sciatic nerve crush, both returning to baseline within seven days. We quantified regeneration in the sciatic nerve by staining for Stathmin-2, a marker of regenerating sensory axons. Our results indicate that PTEN/SOCS3 co-deletion may enhance regenerative branching beyond the injury site. The ultimate goal of this work is to guide therapeutic interventions in cases of peripheral nerve injury with the purpose of improving the lives of millions of individuals who suffer from these injuries each year.