隔日禁食可抑制脊髓损伤中的热蛋白沉积,同时调节胆汁酸代谢并激活 TGR5 信号传导

IF 3.5 3区 医学 Q2 NEUROSCIENCES Frontiers in Molecular Neuroscience Pub Date : 2024-09-12 DOI:10.3389/fnmol.2024.1466125
Honghu Song, Rizhao Pang, Zhixuan Chen, Linjie Wang, Xiaomin Hu, Jingzhi Feng, Wenchun Wang, Jiancheng Liu, Anren Zhang
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引用次数: 0

摘要

隔日禁食(EODF)是一种热量限制形式,在正常进食和禁食之间交替进行,旨在预防和治疗疾病。这种方法已在包括脊髓损伤在内的神经系统疾病的基础研究中得到广泛应用,并已证明具有显著的神经保护作用。此外,EODF 因其安全性和可行性而备受关注,这表明其具有广泛的应用潜力。本研究旨在评估 EODF 对脊髓损伤的治疗效果,并研究和强化其潜在机制。首先,利用 SCI 大鼠模型评估 EODF 对病理损伤和运动功能的影响。随后,考虑到 EODF 对新陈代谢的促进作用,采用液相色谱-质谱法(LC-MS)分析了 SCI 大鼠的胆汁酸代谢,并进一步评估了胆汁酸受体 TGR5 的表达。最终证实,EODF影响了与TGR5信号传导相关的小胶质细胞和NLRP3炎性体的活化,以及下游热蛋白沉积通路相关蛋白和炎性细胞因子的表达,SCI大鼠体内NLRP3/Caspase-1/GSDMD热蛋白沉积通路的活化就是证明。结果表明,EODF 能显著促进 SCI 大鼠运动功能的恢复,减少病理损伤,同时控制体重增加。值得注意的是,EODF促进了胆汁酸代谢产物的分泌,激活了TGR5,抑制了NLRP3/Caspase-1/GSDMD热蛋白沉积通路和炎症。总之,EODF 可通过改善新陈代谢、激活 TGR5 信号传导和抑制 NLRP3 脓毒症通路,减轻 SCI 后的继发性损伤并促进功能恢复。
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Every-other-day fasting inhibits pyroptosis while regulating bile acid metabolism and activating TGR5 signaling in spinal cord injury
Every-other-day fasting (EODF) is a form of caloric restriction that alternates between periods of normal eating and fasting, aimed at preventing and treating diseases. This approach has gained widespread usage in basic research on neurological conditions, including spinal cord injury, and has demonstrated significant neuroprotective effects. Additionally, EODF is noted for its safety and feasibility, suggesting broad potential for application. This study aims to evaluate the therapeutic effects of EODF on spinal cord injury and to investigate and enhance its underlying mechanisms. Initially, the SCI rat model was utilized to evaluate the effects of EODF on pathological injury and motor function. Subsequently, considering the enhancement of metabolism through EODF, bile acid metabolism in SCI rats was analyzed using liquid chromatography-mass spectrometry (LC–MS), and the expression of the bile acid receptor TGR5 was further assessed. Ultimately, it was confirmed that EODF influences the activation of microglia and NLRP3 inflammasomes associated with the TGR5 signaling, along with the expression of downstream pyroptosis pathway related proteins and inflammatory cytokines, as evidenced by the activation of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in SCI rats. The results demonstrated that EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain. Notably, EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats. In summary, EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway.
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来源期刊
CiteScore
5.70
自引率
2.10%
发文量
669
审稿时长
14 weeks
期刊介绍: Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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