Neuron-derived Netrin-1 deficiency aggravates spinal cord injury through activating the NF-κB signaling pathway
Xiaojian Qin,
Xiaolan Zhang,
Xiaodong He,
Hui Xu,
Qiannan Yao,
Zifeng Li,
Yayun Feng,
Yichen Zhong,
Ziyang Li,
Gang Lv,
Yanfeng Wang
Affiliations
Xiaojian Qin
Department of Orthopaedics. The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning Province, China
Xiaolan Zhang
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Xiaodong He
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Hui Xu
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Qiannan Yao
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Zifeng Li
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Yayun Feng
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Yichen Zhong
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China
Ziyang Li
Department of Orthopaedics. The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning Province, China
Gang Lv
Department of Orthopaedics. The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning Province, China; Corresponding author. The First Affiliated Hospital, China Medical University Department: Orthopaedics, BeiEr Road No. 92, Shenyang, Liaoning Province, 110001, China.
Yanfeng Wang
Department of Orthopaedics. The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning Province, China; Corresponding author. The First Affiliated Hospital, China Medical University Department: Orthopaedics, BeiEr Road No. 92, Shenyang, Liaoning Province, 110001, China.
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.
