TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans
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 c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | npj Science of Food |
| Online Access: | https://doi.org/10.1038/s41538-024-00250-5 |
| _version_ | 1797273086328832000 |
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| author | Takahiro Ishimoto Reiya Yamashita Ruri Matsumoto Satoshi Matsumoto Yusuke Matsuo Shunsuke Nakao Yusuke Masuo Makoto Suzuki Yukio Kato |
| author_facet | Takahiro Ishimoto Reiya Yamashita Ruri Matsumoto Satoshi Matsumoto Yusuke Matsuo Shunsuke Nakao Yusuke Masuo Makoto Suzuki Yukio Kato |
| author_sort | Takahiro Ishimoto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:38:33Z |
| format | Article |
| id | doaj.art-22ca57cd6f69492c999acb88d8600b1d |
| institution | Directory Open Access Journal |
| issn | 2396-8370 |
| language | English |
| last_indexed | 2024-03-07T14:38:33Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Science of Food |
| spelling | doaj.art-22ca57cd6f69492c999acb88d8600b1d2024-03-05T20:28:15ZengNature Portfolionpj Science of Food2396-83702024-02-018111310.1038/s41538-024-00250-5TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humansTakahiro Ishimoto0Reiya Yamashita1Ruri Matsumoto2Satoshi Matsumoto3Yusuke Matsuo4Shunsuke Nakao5Yusuke Masuo6Makoto Suzuki7Yukio Kato8Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityL·S Corporation Co. Ltd., 3-10-1 Ningyocho-NihonbashiFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityL·S Corporation Co. Ltd., 3-10-1 Ningyocho-NihonbashiFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityAbstract 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.https://doi.org/10.1038/s41538-024-00250-5 |
| spellingShingle | Takahiro Ishimoto Reiya Yamashita Ruri Matsumoto Satoshi Matsumoto Yusuke Matsuo Shunsuke Nakao Yusuke Masuo Makoto Suzuki Yukio Kato TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans npj Science of Food |
| title | TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans |
| title_full | TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans |
| title_fullStr | TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans |
| title_full_unstemmed | TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans |
| title_short | TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans |
| title_sort | trkb phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans |
| url | https://doi.org/10.1038/s41538-024-00250-5 |
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