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高蛋白饮食下L-茶氨酸通过肝脑轴对神经递质的调节作用及机制

Regulatory Effects and Mechanisms of L-Theanine on Neurotransmitters via Liver-Brain Axis Under a High Protein Diet.

作者信息

Xu Wei, Song Yuxin, Xiao Wenjun, Gong Zhihua

机构信息

Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, 410128, Hunan, China.

National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, 410128, Hunan, China.

出版信息

Mol Neurobiol. 2024 Feb;61(2):783-798. doi: 10.1007/s12035-023-03608-0. Epub 2023 Sep 2.

DOI:10.1007/s12035-023-03608-0
PMID:37659037
Abstract

Excessive protein intake causes liver and brain damage and neurotransmitter disorders, thereby inducing cognitive dysfunction. L-theanine can regulate the neurotransmitter content and show great potential in liver and brain protection. However, it remains unclear whether l-theanine effectively regulates neurotransmitter content under high-protein diet. A 40-day feeding experiment was performed in Sprague Dawley rats to investigate the regulatory effects and mechanisms of l-theanine on neurotransmitters via liver-brain axis in high-protein diets. The results showed that a 30% protein diet increased the liver and brain neurotransmitter content while maintaining the normal structure of liver and the hippocampal CA1 of brain and improving the autonomous behavior of rats. In contrast, 40% and 50% protein diets decreased the content of neurotransmitters, affected autonomous behavior, destroyed the hippocampal CA1 of brain structure, increased hepatic inflammatory infiltration, lipid degeneration, and hepatocyte eosinophilic change in liver, increased liver AST, ALT, MDA, CRP, and blood ammonia level, and decreased liver SOD and CAT level. However, l-theanine improved liver and brain neurotransmitter content, autonomous behavior, liver and hippocampal brain structure, and liver biochemical indicators in 40% and 50% protein diets. To explore how LTA can eliminate the adverse effects of a high-protein diet, we analyzed different metabolites and proteomes and using western blotting for validate quantitatively. We found that l-theanine regulates the activity of PF4 and G protein subunit alpha i2, increases the content of brain-derived neurotrophic factor and dopamine under a 20% protein diet. In addition, l-theanine can activate the adenylate cyclase-protein kinase A pathway through the protein alpha/beta-hydrolase domain protein 12 to regulate the content of neurotransmitters under a 40% protein diet, thereby exerting a neuroprotective effect.

摘要

蛋白质摄入过量会导致肝脏和大脑损伤以及神经递质紊乱,从而诱发认知功能障碍。L-茶氨酸可以调节神经递质含量,并在肝脏和大脑保护方面显示出巨大潜力。然而,尚不清楚L-茶氨酸在高蛋白饮食下是否能有效调节神经递质含量。在斯普拉格-道利大鼠中进行了一项为期40天的喂养实验,以研究L-茶氨酸在高蛋白饮食中通过肝脑轴对神经递质的调节作用及机制。结果表明,30%蛋白质饮食增加了肝脏和大脑神经递质含量,同时维持肝脏的正常结构和大脑海马CA1区,并改善了大鼠的自主行为。相比之下,40%和50%蛋白质饮食降低了神经递质含量,影响了自主行为,破坏了大脑海马CA1区的结构,增加了肝脏的炎性浸润、脂质变性和肝细胞嗜酸性变,提高了肝脏天冬氨酸转氨酶、丙氨酸转氨酶、丙二醛、C反应蛋白和血氨水平,并降低了肝脏超氧化物歧化酶和过氧化氢酶水平。然而,L-茶氨酸改善了40%和50%蛋白质饮食组的肝脏和大脑神经递质含量、自主行为、肝脏和海马大脑结构以及肝脏生化指标。为了探索L-茶氨酸如何消除高蛋白饮食的不利影响,我们分析了不同的代谢物和蛋白质组,并使用蛋白质免疫印迹法进行定量验证。我们发现,L-茶氨酸在20%蛋白质饮食下调节血小板因子4和G蛋白亚基α i2的活性,增加脑源性神经营养因子和多巴胺的含量。此外,L-茶氨酸在40%蛋白质饮食下可通过α/β-水解酶结构域蛋白12激活腺苷酸环化酶-蛋白激酶A途径来调节神经递质含量,从而发挥神经保护作用。

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