首页|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

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Diabetic neuropathic pain(DNP)is the most common disabling complication of diabetes.Emerging evi-dence 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 con-clusion,our studies identified Ntn-3 as an important regula-tor of DNP pathogenesis by gating the aberrant sprouting of sensory axons,indicating that Ntn-3 is a potential druggable target for DNP treatment.

DiabetesDiabetic neuropathic painNetrin-3Axon sprouting

Weiping Pan、Xueyin Huang、Zikai Yu、Qiongqiong Ding、Liping Xia、Jianfeng Hua、Bokai Gu、Qisong Xiong、Hualin Yu、Junbo Wang、Zhenzhong Xu、Linghui Zeng、Ge Bai、Huaqing Liu

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Department of Pharmaceutical Sciences,Zhejiang University City College,Hangzhou 310015,China

College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China

Department of Neurobiology and Department of Neurology of The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China

Department of Anesthesiology and Department of Neurobiology of The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China

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

NHC and CAMS Key Laboratory of Medical Neurobiology,Zhejiang University,Hangzhou 310058,China

Institute of Brain and Cognition,Zhejiang University City College School of Med

Institute of Brain and Cognition,Zhejiang University City College School of Medicine,Hangzhou 310015,China

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Zhejiang Provincial Natural Science Foundation of ChinaScience and Technology Innovation 2030-Major Project of Brain science and Brainlike ResearchExcellent Innovation Program of Hangzhou Municipal University in 2019National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

LY19H0900302021ZD0202501821500039194910431871022

2023

10.1007/s12264-022-01011-8

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(5)
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