Metformin promotes Schwann cell remyelination, preserves neural tissue and improves functional recovery after spinal cord injury

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2023-08-01 DOI:10.1016/j.npep.2023.102348

Zucheng Huang , Junyu Lin (1,) , Hui Jiang , Wanrong Lin , Zhiping Huang , Jiayu Chen , Wende Xiao , Qiong Lin , Jun Wang , Shifeng Wen , Qingan Zhu , Junhao Liu

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引用次数: 0

Abstract

Patients with a spinal cord injury (SCI) usually suffer lifelong disability as a result. Considering this, SCI treatment and pathology study are urgently needed. Metformin, a widely used hypoglycemic drug, has been indicated for its important role in central nervous system diseases. This study aimed to investigate the potential effect of metformin on remyelination after SCI. In the present study, we established a cervical contusion SCI model and metformin treatment was applied after SCI. Biomechanical parameters and behavioral assessment were used to evaluate the severity of injury and the improvement of functional recovery after SCI, respectively. The immunofluorescence and western blot were performed at the terminal time point. Our results showed that treating with metformin after SCI improved functional recovery by reducing the white matter loss and promoting Schwann cell remyelination, and the Nrg1/ErbB signaling pathway may be involved in promoting remyelination mediated by oligodendrocytes and Schwann cells. In addition, the area of spared tissues was significantly increased in the metformin group. However, metformin had no significant effects on the glial scar and inflammation after SCI. In summary, these findings indicated that the role of metformin in Schwann cell remyelination after SCI was probably related to the regulation of the Nrg1/ErbB pathway. It is, therefore, possible to suggest that metformin may be a potential therapy for SCI.

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二甲双胍促进雪旺细胞髓鞘再生，保护神经组织，促进脊髓损伤后功能恢复

脊髓损伤（SCI）患者通常因此而终身残疾。考虑到这一点，迫切需要SCI的治疗和病理学研究。二甲双胍是一种广泛应用的降血糖药物，因其在中枢神经系统疾病中的重要作用而被证明。本研究旨在探讨二甲双胍对SCI后髓鞘再形成的潜在影响。在本研究中，我们建立了一个颈挫伤SCI模型，并在SCI后应用二甲双胍治疗。生物力学参数和行为评估分别用于评估SCI后损伤的严重程度和功能恢复的改善。在终点进行免疫荧光和蛋白质印迹。我们的研究结果表明，SCI后用二甲双胍治疗通过减少白质损失和促进雪旺细胞髓鞘再形成来改善功能恢复，Nrg1/ErbB信号通路可能参与促进少突胶质细胞和雪旺细胞介导的髓鞘再形成。此外，二甲双胍组的备用组织面积显著增加。然而，二甲双胍对SCI后的神经胶质瘢痕和炎症没有显著影响。总之，这些发现表明二甲双胍在SCI后施旺细胞髓鞘再形成中的作用可能与Nrg1/ErbB通路的调节有关。因此，有可能提示二甲双胍可能是一种潜在的SCI治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.