Neuronal death in the dorsal root ganglion after sciatic nerve injury does not depend on sortilin

- Sciatic injury was chosen as PNS injury paradigm to induce DRG neuron cell death.
- Involvement of sortilin was investigated utilizing sortilin-deficient mice.
- A unbiased stereological approach was used to estimate neuron size and number.
- Sortilin deficiency did not prevent injury-induced loss of DRG neurons.
- This implies that pro-neurotrophins do not induce DRG neuron loss through sortilin.

Injury to the sciatic nerve induces loss of sensory neurons in the affected dorsal root ganglia (DRGs). Previous studies have suggested the involvement of the neurotrophin receptors p75 neurotrophin receptor (p75NTR) and sortilin, proposing that sensory neuron subpopulations undergo proneurotrophin-induced apoptosis in a similar manner to what can be observed in the CNS following injury. To further investigate this hypothesis we induced sciatic nerve injury in sortilin-deficient mice, thereby preventing apoptotic signaling of proneurotrophins via the sortilin-p75NTR receptor complex. Using an unbiased stereological approach we found that loss of sortilin did not prevent the injury-induced loss of DRG neurons. This result demonstrates that previous findings linking p75NTR and proneurotrophins to loss of sensory neurons need to involve sortilin-independent pathways and suggests that proneurotrophins may elicit different functions in the CNS and PNS.