Translocator protein alleviates allodynia and improves Schwann cell function against diabetic peripheral neuropathy via activation of the Nrf2‐dependent antioxidant system and promoting autophagy

• DOI: 10.1111/dme.15090
• Publication Date: 2023-03-18T02:18:37Z
• Authors: Nan Gao; Bingjie Ma; Hongbin Jia; Can Hao; Tian Jin; Xiaoming Liu
• Keywords: Allodynia

Abstract Aims In diabetes, autophagy and the nuclear factor erythroid‐derived‐2‐like 2 (Nrf2)‐dependent antioxidant system are impaired. Translocator protein (TSPO) agonist Ro5‐4864 alleviates neuropathic pain, including diabetic peripheral neuropathy (DPN). However, precise mechanisms remain unclear. Thus, we investigated effects of on Nrf2‐dependent in sciatic nerves DPN rats. Methods All rats were randomly assigned to Sham or group. After type diabetes modelling (established by high‐fat diet streptozotocin injection) followed behavioural tests, established group, Ro (TSPO Ro5‐4864) + 3‐MA (autophagy inhibitor) group ML385 (Nrf2 Behavioural assessments performed at baseline, days 3, 7, 14, 21 28. Sciatic collected day 28 for immunofluorescence, morphological western blot analyses. Results alleviated allodynia increased myelin sheath thickness expression after DPN. Beclin‐1 ( p < 0.01) LC3‐II/LC3‐I ratio decreased p62 accumulated administration accumulation. Furthermore, Nrf2 contents cytoplasmic HO‐1 NQO1 expressions significantly inhibited rat, which was also improved Ro5‐4864. beneficial abrogated ML385. Conclusion TSPO exhibited a potent analgesic effect Schwann cell function regeneration against activating promoting autophagy.