Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice

Author:

Cheng Yalan1,Liu Jun1,Luan Yi1,Liu Zhiyuan1,Lai Hejin1,Zhong Wuling1,Yang Yale1,Yu Huimin1,Feng Ning1,Wang Hui1,Huang Rui1,He Zhishui1,Yan Menghong1,Zhang Fang1,Sun Yan-Gang2,Ying Hao1,Guo Feifan1ORCID,Zhai Qiwei13ORCID

Affiliation:

1. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, CAS Center for Excellence in Molecular Cell Sciences, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

2. Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

3. School of Life Science and Technology, ShanghaiTech University, Shanghai, China

Abstract

Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes, but any treatment toward the development of DPN is not yet available. Axon degeneration is an early feature of many peripheral neuropathies, including DPN. Delay of axon degeneration has beneficial effects on various neurodegenerative diseases, but its effect on DPN is yet to be elucidated. Deficiency of Sarm1 significantly attenuates axon degeneration in several models, but the effect of Sarm1 deficiency on DPN is still unclear. In this study, we show that Sarm1 knockout mice exhibit normal glucose metabolism and pain sensitivity, and deletion of the Sarm1 gene alleviates hypoalgesia in streptozotocin-induced diabetic mice. Moreover, Sarm1 gene deficiency attenuates intraepidermal nerve fiber loss in footpad skin; alleviates axon degeneration, the change of g-ratio in sciatic nerves, and NAD+ decrease; and relieves axonal outgrowth retardation of dorsal root ganglia from diabetic mice. In addition, Sarm1 gene deficiency markedly diminishes the changes of gene expression profile induced by streptozotocin in the sciatic nerve, especially some abundant genes involved in neurodegenerative diseases. These findings demonstrate that Sarm1 gene deficiency attenuates DPN in mice and suggest that slowing down axon degeneration is a potential promising strategy to combat DPN.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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