Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder

IF 5.6 1区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Food Science and Human Wellness Pub Date : 2024-09-01 DOI:10.26599/FSHW.2022.9250234

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Abstract

The effective intervention strategy for autism spectrum disorder (ASD) are currently limited. Herein, we attempted to evaluate the potential of L-proline (Pro), a multifunctional amino acid, in ameliorating autism-like behaviors and clarify the molecular mechanisms involved by using the typical valproic acid (VPA)-induced mouse model of ASD. Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice. The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition. The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex (PFC) induced by VPA exposure. RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease, neuroactive ligand-receptor interaction, oxidative phosphorylation, and mitogen activated protein kinase signaling pathway. Overall, dietary Pro supplementation may be a promising intervention strategy for ASD.

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在丙戊酸诱导的自闭症谱系障碍小鼠模型中，补充 L-脯氨酸可改善自闭症样行为并调节肠道微生物群

目前，针对自闭症谱系障碍（ASD）的有效干预策略还很有限。在此，我们尝试使用典型的丙戊酸（VPA）诱导的 ASD 小鼠模型，评估多功能氨基酸 L-脯氨酸（Pro）在改善类似自闭症行为方面的潜力，并阐明其中的分子机制。Pro 能明显减轻 ASD 小鼠的重复行为和社交功能障碍。相关分析表明，Pro 对自闭症样行为的有益影响与肠道微生物群结构和组成的调节有关。组织学分析表明，Pro能逆转VPA暴露引起的前额叶皮层（PFC）Nissl阳性细胞的减少。RNA 测序表明，Pro 还能改变前额叶皮质的转录组特征，具体表现为调节涉及帕金森病、神经活性配体与受体相互作用、氧化磷酸化和丝裂原活化蛋白激酶信号通路的基因。总之，膳食中补充 Pro 可能是一种很有前景的 ASD 干预策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food Science and Human Wellness Agricultural and Biological Sciences-Food Science

CiteScore

8.30

自引率

5.70%

发文量

审稿时长

28 days

期刊介绍： Food Science and Human Wellness is an international peer-reviewed journal that provides a forum for the dissemination of the latest scientific results in food science, nutriology, immunology and cross-field research. Articles must present information that is novel, has high impact and interest, and is of high scientific quality. By their effort, it has been developed to promote the public awareness on diet, advocate healthy diet, reduce the harm caused by unreasonable dietary habit, and directs healthy food development for food industrial producers.