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

作　　者：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 

机构地区：[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 Affliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [5]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 [6]NHC and CAMS Key Laboratory of Medical Neurobiology,Zhejiang University,Hangzhou 310058,China [7]Institute of Brain and Cognition,Zhejiang University City College School of Medicine,Hangzhou 310015,China

出　　处：《Neuroscience Bulletin》2023年第5期745-758,共14页神经科学通报（英文版）

基　　金：supported by the Zhejiang Provincial Natural Science Foundation of China(LY19H090030);the Science and Technology Innovation 2030-Major Project of Brain Science and Brain-like Research(2021ZD0202501);the Excellent Innovation Program of Hangzhou Municipal University in 2019,and the National Natural Science Foundation of China(82150003,91949104,and 31871022).

摘　　要：tDiabetic 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.

关 键 词：Diabetes Diabetic neuropathic pain Netrin-3 Axon sprouting 

分 类 号：R363[医药卫生—病理学]