{"title":"血清细胞外囊泡中的 TrkB 磷酸化与麦角硫因增强人体认知功能有关","authors":"Takahiro Ishimoto, Reiya Yamashita, Ruri Matsumoto, Satoshi Matsumoto, Yusuke Matsuo, Shunsuke Nakao, Yusuke Masuo, Makoto Suzuki, Yukio Kato","doi":"10.1038/s41538-024-00250-5","DOIUrl":null,"url":null,"abstract":"Oral administration of the food-derived antioxidant amino acid ergothioneine (ERGO) results in its efficient distribution in the brain and enhances cognitive function. However, effect of ERGO deficiency on cognitive impairment and the underlying mechanisms remain unknown. We revealed that cognitive function and hippocampal neurogenesis were lower in mice fed an ERGO-free diet than in those fed the control diet. Furthermore, ERGO supplementation to achieve the control diet ERGO levels reversed these effects and restored ERGO concentrations in the plasma and hippocampus. The ERGO-induced recovery of cognitive function and hippocampal neurogenesis was blocked by inhibiting the neurotrophic factor receptor tropomyosin receptor kinase B (TrkB), with a concomitant reduction in hippocampal phosphorylated TrkB, suggesting the involvement of TrkB in these events in mice. Phosphorylated TrkB was also detected in extracellular vesicles (EVs) derived from serum of volunteers who had been orally administered placebo or ERGO-containing tablets. Importantly, the ratio of serum EV-derived phosphorylated TrkB was significantly higher in the ERGO-treated group than in the placebo-treated group and was positively correlated with both serum ERGO concentrations and several cognitive domain scores from Cognitrax. Altogether, TrkB phosphorylation is involved in ERGO-induced cognitive enhancement in mice, and TrkB phosphorylation levels in serum EVs may quantitatively represent ERGO-induced cognitive enhancement in humans.","PeriodicalId":19367,"journal":{"name":"NPJ Science of Food","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41538-024-00250-5.pdf","citationCount":"0","resultStr":"{\"title\":\"TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans\",\"authors\":\"Takahiro Ishimoto, Reiya Yamashita, Ruri Matsumoto, Satoshi Matsumoto, Yusuke Matsuo, Shunsuke Nakao, Yusuke Masuo, Makoto Suzuki, Yukio Kato\",\"doi\":\"10.1038/s41538-024-00250-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Oral administration of the food-derived antioxidant amino acid ergothioneine (ERGO) results in its efficient distribution in the brain and enhances cognitive function. However, effect of ERGO deficiency on cognitive impairment and the underlying mechanisms remain unknown. We revealed that cognitive function and hippocampal neurogenesis were lower in mice fed an ERGO-free diet than in those fed the control diet. Furthermore, ERGO supplementation to achieve the control diet ERGO levels reversed these effects and restored ERGO concentrations in the plasma and hippocampus. The ERGO-induced recovery of cognitive function and hippocampal neurogenesis was blocked by inhibiting the neurotrophic factor receptor tropomyosin receptor kinase B (TrkB), with a concomitant reduction in hippocampal phosphorylated TrkB, suggesting the involvement of TrkB in these events in mice. Phosphorylated TrkB was also detected in extracellular vesicles (EVs) derived from serum of volunteers who had been orally administered placebo or ERGO-containing tablets. Importantly, the ratio of serum EV-derived phosphorylated TrkB was significantly higher in the ERGO-treated group than in the placebo-treated group and was positively correlated with both serum ERGO concentrations and several cognitive domain scores from Cognitrax. 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引用次数: 0
摘要
口服从食物中提取的抗氧化剂氨基酸麦角硫因(ERGO)可使其在大脑中有效分布并增强认知功能。然而,麦角硫因缺乏对认知障碍的影响及其内在机制仍不清楚。我们发现,与对照组相比,喂食不含ERGO食物的小鼠的认知功能和海马神经发生均较低。此外,补充ERGO以达到控制饮食的ERGO水平可逆转这些影响,并恢复血浆和海马中的ERGO浓度。通过抑制神经营养因子受体肌球蛋白受体激酶B(TrkB),ERGO诱导的认知功能和海马神经发生的恢复被阻断,同时海马磷酸化TrkB减少,这表明TrkB参与了小鼠的这些事件。在口服安慰剂或含 ERGO 药片的志愿者血清中提取的细胞外囊泡 (EV) 中也检测到了磷酸化的 TrkB。重要的是,ERGO治疗组血清EV衍生磷酸化TrkB的比率明显高于安慰剂治疗组,并且与血清ERGO浓度和Cognitrax的几个认知领域评分呈正相关。总之,TrkB磷酸化参与了ERGO诱导的小鼠认知能力增强,血清EV中的TrkB磷酸化水平可能定量代表了ERGO诱导的人类认知能力增强。
TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans
Oral administration of the food-derived antioxidant amino acid ergothioneine (ERGO) results in its efficient distribution in the brain and enhances cognitive function. However, effect of ERGO deficiency on cognitive impairment and the underlying mechanisms remain unknown. We revealed that cognitive function and hippocampal neurogenesis were lower in mice fed an ERGO-free diet than in those fed the control diet. Furthermore, ERGO supplementation to achieve the control diet ERGO levels reversed these effects and restored ERGO concentrations in the plasma and hippocampus. The ERGO-induced recovery of cognitive function and hippocampal neurogenesis was blocked by inhibiting the neurotrophic factor receptor tropomyosin receptor kinase B (TrkB), with a concomitant reduction in hippocampal phosphorylated TrkB, suggesting the involvement of TrkB in these events in mice. Phosphorylated TrkB was also detected in extracellular vesicles (EVs) derived from serum of volunteers who had been orally administered placebo or ERGO-containing tablets. Importantly, the ratio of serum EV-derived phosphorylated TrkB was significantly higher in the ERGO-treated group than in the placebo-treated group and was positively correlated with both serum ERGO concentrations and several cognitive domain scores from Cognitrax. Altogether, TrkB phosphorylation is involved in ERGO-induced cognitive enhancement in mice, and TrkB phosphorylation levels in serum EVs may quantitatively represent ERGO-induced cognitive enhancement in humans.
期刊介绍:
npj Science of Food is an online-only and open access journal publishes high-quality, high-impact papers related to food safety, security, integrated production, processing and packaging, the changes and interactions of food components, and the influence on health and wellness properties of food. The journal will support fundamental studies that advance the science of food beyond the classic focus on processing, thereby addressing basic inquiries around food from the public and industry. It will also support research that might result in innovation of technologies and products that are public-friendly while promoting the United Nations sustainable development goals.