神经退行性变卡路里限制对大脑sirtuin蛋白水平的影响

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-09-25 DOI:10.1016/j.bbr.2024.115258

Basar Atalay , Soner Dogan , Burhan Oral Gudu , Elif Yilmaz , Atakan Ayden , Umit Ozorhan , Munevver Burcu Cicekdal , Kaan Yaltirik , Isin Dogan Ekici , Bilge Guvenc Tuna

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引用次数: 0

摘要

背景卡路里限制（CR）被认为能激活神经退行性疾病（NDDs）的保护机制。尽管现有文献强调了 Sirtuin（SIRT）蛋白对年龄相关性神经退行性病变（ND）的保护作用，但还没有研究通过 ELISA 方法同时检测间歇性卡路里限制后脑匀浆中 SIRT 1、3 和 6 蛋白的总含量。我们在小鼠中应用 CR 方案来诱导应激，旨在确定 ND 在自由饮食（AL）或 CR 的情况下是否会更明显。方法：在小鼠基线年龄（BL）为 10 周时，将其随机分配到自由饮食组（AL）、慢性 CR 组（CCR）或间歇 CR 组（ICR）。采用 ELISA 方法测定 49/50 周龄小鼠匀浆全脑上清液中的 SIRT 1、3 和 6 蛋白水平。用甲酚紫对海马的神经元形态进行评估。结果与 AL 组和 BL 组相比，ICR 组的 SIRT1 水平升高。同样，CCR 组的 SIRT1 值也高于 AL 组和 BL 组。虽然与 AL 组和 BL 组相比，ICR 组和 CCR 组的 SIRT3 水平较高，但这一差异未达到统计学意义。与 BL 组和 AL 组相比，ICR 组的 SIRT6 水平也更高，而 CCR 组的 SIRT6 水平也高于 BL 组和 AL 组。图像定量显示，与 CCR 组和 ICR 组相比，AL 组的神经退行性变明显，但未观察到神经细胞形态和数量的改变。结论这项研究表明，脑组织中的 SIRT 1、SIRT 3 和 SIRT 6 水平明显升高，与基线组和自由组相比，持续热量限制组和间歇热量限制组在 50 周时出现 ND 的证据较少。我们的研究结果表明，CR能促进小鼠大脑中SIRT表达的增加，从而有可能减轻神经退行性变。

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Neurodegeneration: Effects of calorie restriction on the brain sirtuin protein levels

Background

Calorie restriction (CR) is suggested to activate protective mechanisms in neurodegenerative diseases (NDDs). Despite existing literature highlighting the protective role of Sirtuin (SIRT) proteins against age-related neurodegeneration (ND), no study has explored the total levels of SIRT 1, 3, and 6 proteins simultaneously in brain homogenates by ELISA following intermittent calorie restriction. Applying CR protocols in mice to induce stress, we aimed to determine whether ND would be more pronounced with ad libitum (AL) or with CR.

Methods

Mice were randomly assigned to ad libitum (AL), Chronic CR (CCR), or Intermittent CR (ICR) groups at 10 weeks of baseline age (BL). SIRT 1, 3, and 6 protein levels were measured in the homogenized whole-brain supernatants of 49/50 weeks old mice by the ELISA method. Neuronal morphology was evaluated by the cresyl violet on the hippocampus. Neurodegeneration (ND) was assessed by the fluoro-jade and ImageJ was used for quantifications.

Results

In the ICR group, SIRT1 levels were elevated compared to both the AL and BL groups. Similarly, the CCR group exhibited higher SIRT1 values compared to the AL and BL groups. While SIRT3 levels were higher in both the ICR and CCR groups compared to the AL and BL groups, this disparity did not reach statistical significance. SIRT6 levels were also higher in the ICR group compared to both the BL and AL groups, with the CCR group showing higher values compared to the BL and AL groups as well. Image quantification demonstrated significant neurodegeneration in the AL group compared to the CCR and ICR group, with no observed alterations in nerve cell morphology and number.

Conclusion

This study revealed that the levels of SIRT 1, SIRT 3, and SIRT 6 in brain tissue were notably elevated, and there was less evidence of ND at the 50-week mark in groups undergoing continuous calorie restriction and intermittent calorie restriction compared to baseline and ad libitum groups. Our findings illustrate that CR promotes increased SIRT expression in the mouse brain, thereby potentially mitigating neurodegeneration.

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.