Frontiers in Cellular Neuroscience (Dec 2023)
The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study
- Chunjia Zhang,
- Chunjia Zhang,
- Chunjia Zhang,
- Chunjia Zhang,
- Chunjia Zhang,
- Yan Li,
- Yan Li,
- Yan Li,
- Fan Bai,
- Fan Bai,
- Fan Bai,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Han Ke,
- Han Ke,
- Han Ke,
- Han Ke,
- Han Ke,
- Han Ke,
- Han Ke,
- Xin Xu,
- Xin Xu,
- Xin Xu,
- Xin Xu,
- Xin Xu,
- Zehui Li,
- Zehui Li,
- Zehui Li,
- Zehui Li,
- Zehui Li,
- Wubo Liu,
- Wubo Liu,
- Wubo Liu,
- Wubo Liu,
- Wubo Liu,
- Wubo Liu,
- Wubo Liu,
- Yunzhu Pan,
- Yunzhu Pan,
- Yunzhu Pan,
- Yunzhu Pan,
- Yunzhu Pan,
- Yunzhu Pan,
- Feng Gao,
- Feng Gao,
- Feng Gao,
- Feng Gao,
- Feng Gao,
- Degang Yang,
- Degang Yang,
- Degang Yang,
- Degang Yang,
- Degang Yang,
- Xiaoxin Wang,
- Xiaoxin Wang,
- Xiaoxin Wang,
- Xiaoxin Wang,
- Xiaoxin Wang,
- Huayong Du,
- Huayong Du,
- Huayong Du,
- Huayong Du,
- Huayong Du,
- Shuang Guo,
- Shuang Guo,
- Shuang Guo,
- Shuang Guo,
- Shuang Guo,
- Han Gong,
- Han Gong,
- Han Gong,
- Han Gong,
- Han Gong,
- Liangjie Du,
- Liangjie Du,
- Liangjie Du,
- Liangjie Du,
- Liangjie Du,
- Yan Yu,
- Yan Yu,
- Yan Yu,
- Yan Yu,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li
Affiliations
- Chunjia Zhang
- School of Rehabilitation, Capital Medical University, Beijing, China
- Chunjia Zhang
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Chunjia Zhang
- China Rehabilitation Science Institute, Beijing, China
- Chunjia Zhang
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Chunjia Zhang
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Yan Li
- China Rehabilitation Science Institute, Beijing, China
- Yan Li
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Yan Li
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Fan Bai
- China Rehabilitation Science Institute, Beijing, China
- Fan Bai
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Fan Bai
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Zuliyaer Talifu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Zuliyaer Talifu
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Zuliyaer Talifu
- China Rehabilitation Science Institute, Beijing, China
- Zuliyaer Talifu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Zuliyaer Talifu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Zuliyaer Talifu
- School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, China
- Han Ke
- School of Rehabilitation, Capital Medical University, Beijing, China
- Han Ke
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Han Ke
- China Rehabilitation Science Institute, Beijing, China
- Han Ke
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Han Ke
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Han Ke
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Han Ke
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Xin Xu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Xin Xu
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Xin Xu
- China Rehabilitation Science Institute, Beijing, China
- Xin Xu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Xin Xu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Zehui Li
- School of Rehabilitation, Capital Medical University, Beijing, China
- Zehui Li
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Zehui Li
- China Rehabilitation Science Institute, Beijing, China
- Zehui Li
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Zehui Li
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Wubo Liu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Wubo Liu
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Wubo Liu
- China Rehabilitation Science Institute, Beijing, China
- Wubo Liu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Wubo Liu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Wubo Liu
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Wubo Liu
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Yunzhu Pan
- School of Rehabilitation, Capital Medical University, Beijing, China
- Yunzhu Pan
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Yunzhu Pan
- China Rehabilitation Science Institute, Beijing, China
- Yunzhu Pan
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Yunzhu Pan
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Yunzhu Pan
- School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, China
- Feng Gao
- School of Rehabilitation, Capital Medical University, Beijing, China
- Feng Gao
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Feng Gao
- China Rehabilitation Science Institute, Beijing, China
- Feng Gao
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Feng Gao
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Degang Yang
- School of Rehabilitation, Capital Medical University, Beijing, China
- Degang Yang
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Degang Yang
- China Rehabilitation Science Institute, Beijing, China
- Degang Yang
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Degang Yang
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Xiaoxin Wang
- School of Rehabilitation, Capital Medical University, Beijing, China
- Xiaoxin Wang
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Xiaoxin Wang
- China Rehabilitation Science Institute, Beijing, China
- Xiaoxin Wang
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Xiaoxin Wang
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Huayong Du
- School of Rehabilitation, Capital Medical University, Beijing, China
- Huayong Du
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Huayong Du
- China Rehabilitation Science Institute, Beijing, China
- Huayong Du
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Huayong Du
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Shuang Guo
- School of Rehabilitation, Capital Medical University, Beijing, China
- Shuang Guo
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Shuang Guo
- China Rehabilitation Science Institute, Beijing, China
- Shuang Guo
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Shuang Guo
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Han Gong
- School of Rehabilitation, Capital Medical University, Beijing, China
- Han Gong
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Han Gong
- China Rehabilitation Science Institute, Beijing, China
- Han Gong
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Han Gong
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Liangjie Du
- School of Rehabilitation, Capital Medical University, Beijing, China
- Liangjie Du
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Liangjie Du
- China Rehabilitation Science Institute, Beijing, China
- Liangjie Du
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Liangjie Du
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Yan Yu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Yan Yu
- China Rehabilitation Science Institute, Beijing, China
- Yan Yu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Yan Yu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Jianjun Li
- School of Rehabilitation, Capital Medical University, Beijing, China
- Jianjun Li
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Jianjun Li
- China Rehabilitation Science Institute, Beijing, China
- Jianjun Li
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Jianjun Li
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Jianjun Li
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- DOI
- https://doi.org/10.3389/fncel.2023.1323566
- Journal volume & issue
-
Vol. 17
Abstract
BackgroundNicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated.MethodsWe established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR.ResultsNMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1β (IL-1β), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1β, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI.ConclusionThe reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.
Keywords
- spinal cord injury
- nicotinamide mononucleotide
- inflammation
- signaling pathway
- transcriptome sequencing technology
