Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons.
10.1007/s12264-022-01011-8
- Author:
Weiping PAN
1
;
Xueyin HUANG
2
;
Zikai YU
1
;
Qiongqiong DING
1
;
Liping XIA
3
;
Jianfeng HUA
2
;
Bokai GU
2
;
Qisong XIONG
1
;
Hualin YU
1
;
Junbo WANG
1
;
Zhenzhong XU
3
;
Linghui ZENG
1
;
Ge BAI
4
;
Huaqing LIU
5
Author Information
1. Department of Pharmaceutical Sciences, Zhejiang University City College, Hangzhou, 310015, China.
2. Department of Neurobiology and Department of Neurology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
3. Department of Anesthesiology and Department of Neurobiology of The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
4. Department of Neurobiology and Department of Neurology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. gebai@zju.edu.cn.
5. Department of Pharmaceutical Sciences, Zhejiang University City College, Hangzhou, 310015, China. liuhq@zucc.edu.cn.
- Publication Type:Journal Article
- Keywords:
Axon sprouting;
Diabetes;
Diabetic neuropathic pain;
Netrin-3
- MeSH:
Mice;
Animals;
Diabetes Mellitus, Experimental/metabolism*;
Axons/physiology*;
Diabetic Neuropathies;
Sensory Receptor Cells/metabolism*;
Neuralgia/metabolism*
- From:
Neuroscience Bulletin
2023;39(5):745-758
- CountryChina
- Language:English
-
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.
