Prophylactic Effects of Betaine on Depression and Anxiety Behaviors in Mice with Dextran Sulfate Sodium-Induced Colitis,Journal of Agricultural and Food Chemistry

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Prophylactic Effects of Betaine on Depression and Anxiety Behaviors in Mice with Dextran Sulfate Sodium-Induced Colitis
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-14 , DOI: 10.1021/acs.jafc.4c05547
Wenjia Liu _{1,

2,

3} , Xiaolin Zhong ₁ , Yan Yi ₄ , Lihua Xie _{1,

3} , Wenyan Zhou ₁ , Wenyu Cao ₂ , Ling Chen ₁

Affiliation

Ulcerative colitis (UC) is a typical type of inflammatory bowl disease, which is accompanied by an increased risk of depression and anxiety-related psychological symptoms. Betaine is a naturally derived compound that can function as an anti-inflammatory drug and a neuromodulator. In-depth exploration of the potential role of betaine in treating UC-related depression and anxiety is crucial. This study aimed to elucidate the effects of betaine on UC-related depression and anxiety and clarify the underlying mechanisms. A dextran sulfate sodium (DSS)-induced mice model was established by 4% DSS drinking ad libitum for 7 days. The colonic injury was measured using hematoxylin-eosin (HE) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining. Depression and anxiety-like behaviors were separately evaluated using a forced swimming test (FST), a tail suspension test (TST), a light-dark box test (LDBT), and an open field test (OFT). Immunohistochemistry was used to detect DNA damage and neurogenesis in the hippocampus. Western blotting was applied to detect the protein levels of macrophage polarization in mice colons and the alteration of mitochondrial dysfunction and the cGAS-STING pathway in the hippocampus. Betaine strongly alleviated mucosal structural disorder and mucin secretion reduction and promoted M2-macrophage polarization in the colon of DSS-treated mice. In addition, betaine could mitigate depression- and anxiety-like behaviors in DSS-treated mice, reduce the DNA damage and mitochondrial dysfunction, and inhibit the cGAS-STING signaling pathway. Our study reveals the antidepression/anxiety effects of betaine and further demonstrates the potential mechanism by which betaine inhibits DNA damage and mitochondrial dysfunction to block the cGAS-STING pathway, thereby repairing neurogenesis in the hippocampus.

中文翻译：

甜菜碱对右旋糖酐硫酸钠诱导的结肠炎小鼠抑郁和焦虑行为的预防作用

溃疡性结肠炎（UC）是一种典型的炎症性肠病，伴有抑郁和焦虑相关心理症状的风险增加。甜菜碱是一种天然化合物，可用作抗炎药和神经调节剂。深入探索甜菜碱在治疗 UC 相关抑郁和焦虑中的潜在作用至关重要。本研究旨在阐明甜菜碱对 UC 相关抑郁和焦虑的影响并阐明其潜在机制。采用4%DSS随意饮水7d建立小鼠模型。使用苏木精-伊红（HE）染色和阿新蓝-高碘酸希夫（AB-PAS）染色测量结肠损伤。使用强迫游泳测试（FST）、悬尾测试（TST）、明暗盒测试（LDBT）和旷场测试（OFT）分别评估抑郁和焦虑样行为。免疫组织化学用于检测海马体中的 DNA 损伤和神经发生。采用Western blotting检测小鼠结肠巨噬细胞极化的蛋白水平以及海马线粒体功能障碍和cGAS-STING通路的改变。甜菜碱强烈缓解 DSS 处理小鼠结肠中的粘膜结构紊乱和粘蛋白分泌减少，并促进 M2-巨噬细胞极化。此外，甜菜碱可以减轻 DSS 治疗小鼠的抑郁和焦虑样行为，减少 DNA 损伤和线粒体功能障碍，并抑制 cGAS-STING 信号通路。我们的研究揭示了甜菜碱的抗抑郁/焦虑作用，并进一步证明了甜菜碱抑制DNA损伤和线粒体功能障碍从而阻断cGAS-STING通路，从而修复海马神经发生的潜在机制。

更新日期：2024-09-14

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