Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
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Sarm1 基因缺陷可减轻小鼠糖尿病周围神经病变
DOI：
10.2337/db18-1233
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发表时间：
2019-11-01
期刊：
影响因子：
7.7
通讯作者：
Zhai, Qiwei
中科院分区：
文献类型：
--
作者：
Cheng, Yalan;Liu, Jun;Zhai, Qiwei
糖尿病周围神经病变（DPN）是1型和2型糖尿病中最常见的并发症，但尚未有任何治疗DPN的方法。轴突变性是包括DPN在内的许多周围神经病变的早期特征。延迟轴突变性对各种神经退行性疾病具有有益作用，但其对DPN的作用尚未阐明。在几种模型中，Sarm 1的缺陷显著减弱了轴突变性，但Sarm 1缺陷对DPN的影响仍不清楚。在这项研究中，我们表明Sarm 1基因敲除小鼠表现出正常的葡萄糖代谢和疼痛敏感性，并且Sarm 1基因的缺失可以缓解链脲佐菌素诱导的糖尿病小鼠的痛觉减退。此外，Sarm 1基因缺陷可减轻足垫皮肤表皮内神经纤维丢失;减轻轴突变性、坐骨神经g-比率改变和NAD+减少;缓解糖尿病小鼠背根神经节轴突生长迟缓。此外，SARM 1基因缺陷明显减少了链脲佐菌素诱导的坐骨神经基因表达谱的变化，特别是一些丰富的参与神经退行性疾病的基因。这些发现表明，Sarm 1基因缺陷减弱了小鼠的DPN，并表明减缓轴突变性是对抗DPN的潜在有希望的策略。
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.