Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-08-14 DOI:10.1016/j.brainresbull.2025.111510

Hui Ni , Weiping Sha , Tianli Xu , Qiancheng Zhu , Qun Huang , Jin Wang , Qi Gu , Yi Zhu , Liming Wang , Shoujin Tian , Rong Gao , Jianfei Ge , Xiaolong Lin

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引用次数: 0

Abstract

Spinal cord injury (SCI), a traumatic condition affecting the nervous system, constitutes an orthopedic emergency that is closely associated with a significantly elevated disability rate. Excessive apoptosis not only hinders neuronal repair, but also exacerbates the deterioration of the local microenvironment, thereby impeding the treatment of SCI. The present study comprehensively investigated the dynamic expression of mitochondrial deacetylase sirtuin 3 (SIRT3) in a murine model of SCI. Activation of SIRT3 with the natural agonist honokiol (HKL) facilitated neurological functional recovery by mitigating neuronal apoptosis and oxidative stress injury in vivo. Mechanistically, through comparative analysis of transcriptome alterations after global deletion of SIRT3 (Sirt3^-/-), mitochondrion localized protein peroxidase peroxiredoxin 5 (PRDX5) was identified as the direct downstream effector of SIRT3. Spatially, SIRT3 and PRDX5 were colocalized within neurons in the anterior horn of the spinal cord. Genetic silencing of PRDX5 partially attenuated the protective effects of SIRT3 against neuronal apoptosis and the promotion of functional recovery. Overall, this study is the first to reveal the pivotal role of the SIRT3PRDX5 axis in modulating neuronal apoptosis after SCI, and thus offers a novel perspective on the restoration of function after SCI.

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SIRT3 / PRDX5信号的激活抑制小鼠急性脊髓损伤后的细胞凋亡

脊髓损伤（SCI）是一种影响神经系统的创伤性疾病，是与致残率显著升高密切相关的骨科急症。过度的细胞凋亡不仅阻碍神经元修复，还会加剧局部微环境的恶化，从而阻碍脊髓损伤的治疗。本研究全面研究了线粒体去乙酰化酶sirtuin 3 （SIRT3）在脊髓损伤小鼠模型中的动态表达。天然激动剂檀香醇（HKL）激活SIRT3通过减轻神经元凋亡和氧化应激损伤促进神经功能恢复。机制上，通过对SIRT3全局缺失（SIRT3 -/-）后转录组改变的比较分析，确定线粒体定位蛋白过氧化物酶过氧化物还蛋白5 （PRDX5）是SIRT3的直接下游效应物。在空间上，SIRT3和PRDX5共定位于脊髓前角的神经元内。PRDX5基因沉默部分减弱了SIRT3对神经元凋亡的保护作用和促进功能恢复的作用。总的来说，本研究首次揭示了SIRT3PRDX5轴在脊髓损伤后神经元凋亡调控中的关键作用，为脊髓损伤后功能恢复提供了新的视角。

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

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.