TNF-α Promotes the Recovery of Dorsal Root Ganglion Neurons from Cisplatin-Induced Injury Through an NGF-Independent Mechanism

TL;DR

This study shows that TNF-α helps injured neurons recover from chemotherapy damage through a mechanism not involving NGF.

Contribution

The novel finding is that TNF-α promotes neuron recovery via TNFR2 and NF-κB, independently of NGF.

Findings

TNF-α promotes neurite regeneration in cisplatin-injured DRG neurons.

TNF-α accelerates DNA damage removal and mitochondrial regeneration in DRG neurons.

The effect of TNF-α is mediated through TNFR2 and NF-κB activation, not NGF signaling.

Abstract

Nerve injury caused by chemotherapy drugs is a common side effect. How to reduce this kind of nerve injury and promote neuron recovery is of great significance. In this study, we found that tumor necrosis factor-α (TNF-α) promoted the recovery of dorsal root ganglion (DRG) neuron from cisplatin-induced injury. On DRG neurons cultured in vitro, we found that TNF-α promoted neurite regeneration after cisplatin injury. In addition, TNF-α accelerated the removal of DNA damage and promoted the regeneration of mitochondria on DRG neurons. Study of the mechanism showed that this effect of TNF-α was independent from the NGF signaling pathway and occurred mostly through the activation of TNFR2 receptors, together with nucleus translocation of p65 and upregulation of NF-κB expression. This study provides a new theoretical basis and therapeutic strategy for the treatment of nerve injury caused by chemotherapy drugs.

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