Neuron-derived Netrin-1 deficiency aggravates spinal cord injury through activating the NF-κB signaling pathway.

Netrin-1 (NTN1) is involved in psychological alterations caused by central nerve system diseases. The primary objective of this research was to investigate whether a deficiency of neuron-derived NTN1 in the remote brain regions affects SCI outcomes. To examine the roles and mechanisms of neuron-derived NTN1 during SCI, Western blots, Nissl staining, immunochemical technique, RNA-sequence, and related behavioral tests were conducted in the study. Our study revealed that mice lacking NTN1 exhibited normal morphological structure of the spinal cords, hippocampus, and neurological function. While neuron-derived NTN1deletion mechanistically disrupted neuronal regeneration and aggregates neuronal apoptosis and ferroptosis in the intermediate phase following SCI. Additionally, neuroinflammation was significantly enhanced in the early phase, which could be related to activation of the NF-κB signaling pathway. Overall, our findings indicate that the deletion of neuron-derived NTN1 leads to the activation of the NF-κB pathway, contributing to the promotion of neuronal apoptosis and ferroptosis, and the pathological progression of SCI.