2. Academic Validation
  3. Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons

Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons

  • Neurosci Bull. 2023 Jan 1. doi: 10.1007/s12264-022-01011-8.
Weiping Pan # 1 2,  Xueyin Huang # 3,  Zikai Yu # 1 2,  Qiongqiong Ding 1,  Liping Xia 4,  Jianfeng Hua 3,  Bokai Gu 3,  Qisong Xiong 1 2,  Hualin Yu 1 2,  Junbo Wang 1,  Zhenzhong Xu 4,  Linghui Zeng 1,  Ge Bai 5 6 7 8,  Huaqing Liu 9 10
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, Zhejiang University City College, Hangzhou, 310015, China.
  • 2 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 3 Department of Neurobiology and Department of Neurology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 4 Department of Anesthesiology and Department of Neurobiology of The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 5 Department of Neurobiology and Department of Neurology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. gebai@zju.edu.cn.
  • 6 Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China. gebai@zju.edu.cn.
  • 7 NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China. gebai@zju.edu.cn.
  • 8 Institute of Brain and Cognition, Zhejiang University City College School of Medicine, Hangzhou, 310015, China. gebai@zju.edu.cn.
  • 9 Department of Pharmaceutical Sciences, Zhejiang University City College, Hangzhou, 310015, China. liuhq@zucc.edu.cn.
  • 10 Institute of Brain and Cognition, Zhejiang University City College School of Medicine, Hangzhou, 310015, China. liuhq@zucc.edu.cn.
  • # Contributed equally.
PMID: 36587114 DOI: 10.1007/s12264-022-01011-8
Abstract

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.

Keywords

Axon sprouting; Diabetes; Diabetic neuropathic pain; Netrin-3.

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