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口服中链脂肪酸癸酸对成年雄性 C57BL/6J 小鼠运动活动及焦虑样和抑郁相关行为的急慢性影响。

Acute and chronic effects of oral administration of a medium-chain fatty acid, capric acid, on locomotor activity and anxiety-like and depression-related behaviors in adult male C57BL/6J mice.

机构信息

Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.

Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Japan.

出版信息

Neuropsychopharmacol Rep. 2022 Mar;42(1):59-69. doi: 10.1002/npr2.12226. Epub 2022 Jan 7.

Abstract

AIM

Capric acid (also known as decanoic acid or C10) is one of the fatty acids in the medium-chain triglycerides (MCTs) commonly found in dietary fats. Although dietary treatment with MCTs is recently of great interest for the potential therapeutic effects on neuropsychiatric disorders, the effects of oral administration of C10 on behavior remain to be examined. This study investigated acute and chronic effects of oral administration of C10 on locomotor activity and anxiety-like and depression-related behaviors in adult male C57BL/6J mice.

METHODS

To explore the acute effects of C10 administration, mice were subjected to a series of behavioral tests in the following order: light/dark transition, open field, elevated plus maze, Porsolt forced swim, and tail suspension tests, 30 minutes after oral gavage of either vehicle or C10 solution (30 mmol/kg dose in Experiment 1; 0.1, 0.3, 1.0, 3.0 mmol/kg doses in Experiment 2). Next, to examine chronic effects of C10, mice repeatedly administered with either vehicle or C10 solution (0.3, 3.0 mmol/kg doses per day, for 21 days, in Experiment 3) were subjected to behavioral tests without oral administration immediately before each test.

RESULTS

The mice administrated with the high dose of C10 (30 mmol/kg) showed lower body weights, shorter distance traveled, and more anxiety-like behavior than vehicle-treated mice, and the results reached study-wide statistical significance. The C10 administration at a lower dose of 0.3 mmol/kg had no significant effects on body weights and induced nominally significantly longer distance traveled than vehicle administration. Repeated administration of C10 at a dose of 3.0 mmol/kg for more than 21 days caused lower body weights and decreased depression-related behavior, although the behavioral differences did not reach study-wide significance.

CONCLUSIONS

Although these results suggest dose-dependent effects of oral administration of capric acid on locomotor activity and anxiety-like and depression-related behaviors, further study will be needed to replicate the findings and explore the underlying brain mechanisms.

摘要

目的

癸酸(也称为癸酸或 C10)是中链甘油三酯(MCT)中常见的脂肪酸之一,存在于膳食脂肪中。尽管 MCT 的饮食治疗最近因其对神经精神疾病的潜在治疗效果而备受关注,但口服 C10 对行为的影响仍有待研究。本研究探讨了口服 C10 对成年雄性 C57BL/6J 小鼠运动活动以及焦虑样和抑郁相关行为的急性和慢性影响。

方法

为了探索 C10 给药的急性作用,在口服灌胃后 30 分钟内,按照以下顺序对小鼠进行一系列行为测试:明暗过渡、旷场、高架十字迷宫、强迫游泳和悬尾测试,实验组给予载体或 C10 溶液(剂量为 30mmol/kg;实验组给予载体或 C10 溶液(剂量为 0.1、0.3、1.0、3.0mmol/kg;实验组给予载体或 C10 溶液(剂量为 0.3、3.0mmol/kg,每天一次,连续 21 天,在实验 3 中,在每次测试前不进行口服给药)。

结果

给予高剂量 C10(30mmol/kg)的小鼠比给予载体的小鼠体重更轻、行走距离更短、表现出更明显的焦虑样行为,结果达到研究范围的统计学意义。C10 以低剂量 0.3mmol/kg 给药对体重没有显著影响,并诱导名义上比载体给药更长的行走距离。重复给予 C10 剂量为 3.0mmol/kg 超过 21 天会导致体重降低和抑郁相关行为减少,尽管行为差异没有达到研究范围的统计学意义。

结论

尽管这些结果表明口服癸酸对运动活动以及焦虑样和抑郁相关行为有剂量依赖性影响,但需要进一步研究来复制这些发现并探索潜在的大脑机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f273/8919109/7d6978108ecf/NPR2-42-59-g002.jpg

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