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生酮饮食对杜氏肌营养不良症生化和临床参数评估的影响:临床前研究。

Effects of a Ketogenic Diet on the Assessment of Biochemical and Clinical Parameters in Duchenne Muscular Dystrophy: A Preclinical Investigation.

机构信息

Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, Palhoça, SC, 88137-270, Brazil.

University of West Santa Catarina, Joaçaba, SC, Brazil.

出版信息

Mol Neurobiol. 2024 Dec;61(12):10992-11011. doi: 10.1007/s12035-024-04258-6. Epub 2024 May 31.

DOI:10.1007/s12035-024-04258-6
PMID:38816675
Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive skeletal muscle degeneration and systemic effects, including the central nervous system (CNS). This study aimed to assess the impact of a 14-day ketogenic diet (DCet) on biochemical and clinical parameters in a DMD mouse model. Young adult mice (50 days old) were fed DCet, while control groups received a standard diet. On the 14th day, memory and behavior tests were conducted, followed by biochemical evaluations of oxidative stress, inflammatory biomarkers, body weight, feed intake, and brain-derived neurotrophic factor (BDNF) levels. mdx + DCet mice showed reduced mass (0.2 g ± 2.49) and improved memory retention (p < 0.05) compared to controls. Oxidative damage in muscle tissue and CNS decreased, along with a significant cytokine level reduction (p <0.05). The protocol led to an increase in hippocampal BDNF and mitochondrial respiratory complex activity in muscle tissue and the central nervous system (CNS), while also decreasing creatine kinase activity only in the striatum. Overall, a 14-day DCet showed protective effects by improving spatial learning and memory through reductions in oxidative stress and immune response, as well as increases in BDNF levels, consistent with our study's findings.

摘要

杜氏肌营养不良症(DMD)是一种 X 连锁隐性遗传病,其特征是进行性骨骼肌退化和全身性影响,包括中枢神经系统(CNS)。本研究旨在评估 14 天生酮饮食(DCet)对 DMD 小鼠模型生化和临床参数的影响。年轻成年小鼠(50 天大)喂食 DCet,而对照组则喂食标准饮食。在第 14 天,进行记忆和行为测试,然后对氧化应激、炎症生物标志物、体重、饲料摄入量和脑源性神经营养因子(BDNF)水平进行生化评估。与对照组相比,mdx + DCet 小鼠的体重(0.2 克±2.49)降低,记忆保留能力提高(p <0.05)。肌肉组织和中枢神经系统中的氧化损伤减少,细胞因子水平显著降低(p <0.05)。该方案导致海马 BDNF 和肌肉组织及中枢神经系统(CNS)中线粒体呼吸复合物活性增加,同时仅纹状体肌酸激酶活性降低。总之,14 天的 DCet 通过降低氧化应激和免疫反应以及增加 BDNF 水平来改善空间学习和记忆,从而显示出保护作用,这与我们的研究结果一致。

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Spatiotemporal diversity in molecular and functional abnormalities in the mdx dystrophic brain.mdx 营养不良性大脑中分子和功能异常的时空多样性。
Mol Med. 2025 Mar 20;31(1):108. doi: 10.1186/s10020-025-01109-5.
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The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging.线粒体疗法在治疗衰老过程中的氧化应激和炎症方面的潜力。

本文引用的文献

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Exercise and Dietary Factors Mediate Neural Plasticity Through Modulation of BDNF Signaling.运动和饮食因素通过调节脑源性神经营养因子(BDNF)信号传导介导神经可塑性。
Brain Plast. 2022 Oct 21;8(1):121-128. doi: 10.3233/BPL-220140. eCollection 2022.
2
BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults.脑源性神经营养因子介导健康老年人进行计算机化认知训练后认知能力的改善。
Alzheimers Dement (N Y). 2022 Aug 30;8(1):e12337. doi: 10.1002/trc2.12337. eCollection 2022.
3
Inflammation in Duchenne Muscular Dystrophy-Exploring the Role of Neutrophils in Muscle Damage and Regeneration.
Mol Neurobiol. 2025 Jun;62(6):6748-6763. doi: 10.1007/s12035-024-04474-0. Epub 2024 Sep 4.
杜氏肌营养不良症中的炎症——探索中性粒细胞在肌肉损伤和再生中的作用
Biomedicines. 2021 Oct 1;9(10):1366. doi: 10.3390/biomedicines9101366.
4
Ketogenic diet with medium-chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy.生酮饮食联合中链甘油三酯可恢复杜氏肌营养不良症大鼠模型的骨骼肌功能和病理。
FASEB J. 2021 Sep;35(9):e21861. doi: 10.1096/fj.202100629R.
5
Swimming Improves Memory and Antioxidant Defense in an Animal Model of Duchenne Muscular Dystrophy.游泳可改善杜氏肌营养不良症动物模型的记忆和抗氧化防御能力。
Mol Neurobiol. 2021 Oct;58(10):5067-5077. doi: 10.1007/s12035-021-02482-y. Epub 2021 Jul 10.
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Duchenne muscular dystrophy.杜氏肌营养不良症。
Nat Rev Dis Primers. 2021 Feb 18;7(1):13. doi: 10.1038/s41572-021-00248-3.
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