Despite the ability of peripheral nerves to spontaneously regenerate after injury, recovery is generally very poor. The neurotrophins have emerged as an important modulator of axon regeneration, particularly brain derived neurotrophic factor (BDNF). BDNF regulation and signaling, as well as its role in activity-dependent treatments including electrical stimulation, exercise, and optogenetic stimulation are discussed here. The importance of a single nucleotide polymorphism in the BDNF gene, Val66Met, which is present in 30% of the human population and may hinder the efficacy of these treatments in enhancing regeneration after injury is considered. Preliminary data are presented on the effectiveness of one such activity-dependent treatment, electrical stimulation, in enhancing axon regeneration in mice expressing the met allele of the Val66Met polymorphism.
Keywords: BDNF; Val66Met; electrical stimulation; exercise; optogenetics; peripheral nerve injury; trkB.