The SELENOT mimetic PSELT promotes nerve regeneration by increasing axonal myelination in a facial nerve injury model in female rats

Peripheral nerve injury (PNI) is frequent and many patients suffer lifelong disabilities in severe cases. Although the peripheral nervous system is able to regenerate, its potential is limited. In this study, we tested in a nerve regeneration model in rat the potential beneficial effect of a short mimetic peptide, named PSELT, which derives from SELENOT, an essential thioredoxin‐like selenoprotein endowed with neuroprotective and antioxidant activities. For this purpose, the right facial nerve of female Long–Evans rats was axotomized then bridged with a free femoral vein interposition graft. PSELT (1 μM) was injected into the vein immediately and 48 h after the injury, and the effects observed were compared to those found after an end‐to‐end suture used as a gold standard treatment. Whisking behavior, electrophysiological potential, and histological analyses were performed 3 months after injury to determine the effects of these treatments. These analyses revealed that PSELT‐treated animals exhibit a better motor recovery in terms of protraction amplitude and velocity of vibrissae compared to control and end‐sutured nerve animal groups. Moreover, administration of PSELT following injury enhanced muscle innervation, axonal elongation, and myelination of newly formed nerve fibers. Altogether, these results indicate that a PSELT‐based treatment is sufficient to enhance facial nerve myelination and regeneration and could represent a new therapeutic tool to treat PNI.