Brain-transportable dipeptides across the blood-brain barrier in mice

Apart from nutrients required for the brain, there has been no report that naturally occurring peptides can cross the blood-brain barrier (BBB). The aim of this study was to identify the BBB-transportable peptides using in situ mouse perfusion experiments. Based on the structural features of Gly-N-m...

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Autores principales: Tanaka, Mitsuru, Dohgu, Shinya, Komabayashi, Genki, Kiyohara, Hayato, Takata, Fuyuko, Kataoka, Yasufumi, Nirasawa, Takashi, Maebuchi, Motohiro, Matsui, Toshiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453885/
https://www.ncbi.nlm.nih.gov/pubmed/30962462
http://dx.doi.org/10.1038/s41598-019-42099-9
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author Tanaka, Mitsuru
Dohgu, Shinya
Komabayashi, Genki
Kiyohara, Hayato
Takata, Fuyuko
Kataoka, Yasufumi
Nirasawa, Takashi
Maebuchi, Motohiro
Matsui, Toshiro
author_facet Tanaka, Mitsuru
Dohgu, Shinya
Komabayashi, Genki
Kiyohara, Hayato
Takata, Fuyuko
Kataoka, Yasufumi
Nirasawa, Takashi
Maebuchi, Motohiro
Matsui, Toshiro
author_sort Tanaka, Mitsuru
collection PubMed
description Apart from nutrients required for the brain, there has been no report that naturally occurring peptides can cross the blood-brain barrier (BBB). The aim of this study was to identify the BBB-transportable peptides using in situ mouse perfusion experiments. Based on the structural features of Gly-N-methylated Gly (Gly-Sar), a reported BBB-transportable compound, 18 dipeptides were synthesized, and were perfused in the mouse brain for two minutes. Among the synthesized dipeptides, Gly-Sar, Gly-Pro, and Tyr-Pro were transported across the BBB with K(i) values of 7.60 ± 1.29, 3.49 ± 0.66, and 3.53 ± 0.74 µL/g·min, respectively, and accumulated in the mouse brain parenchyma. Additionally, using MALDI-MS/MS imaging analysis of Tyr-Pro-perfused brain, we provide evidence for Tyr-Pro accumulation in the hippocampus, hypothalamus, striatum, cerebral cortex, and cerebellum of mouse brain.
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spelling pubmed-64538852019-04-12 Brain-transportable dipeptides across the blood-brain barrier in mice Tanaka, Mitsuru Dohgu, Shinya Komabayashi, Genki Kiyohara, Hayato Takata, Fuyuko Kataoka, Yasufumi Nirasawa, Takashi Maebuchi, Motohiro Matsui, Toshiro Sci Rep Article Apart from nutrients required for the brain, there has been no report that naturally occurring peptides can cross the blood-brain barrier (BBB). The aim of this study was to identify the BBB-transportable peptides using in situ mouse perfusion experiments. Based on the structural features of Gly-N-methylated Gly (Gly-Sar), a reported BBB-transportable compound, 18 dipeptides were synthesized, and were perfused in the mouse brain for two minutes. Among the synthesized dipeptides, Gly-Sar, Gly-Pro, and Tyr-Pro were transported across the BBB with K(i) values of 7.60 ± 1.29, 3.49 ± 0.66, and 3.53 ± 0.74 µL/g·min, respectively, and accumulated in the mouse brain parenchyma. Additionally, using MALDI-MS/MS imaging analysis of Tyr-Pro-perfused brain, we provide evidence for Tyr-Pro accumulation in the hippocampus, hypothalamus, striatum, cerebral cortex, and cerebellum of mouse brain. Nature Publishing Group UK 2019-04-08 /pmc/articles/PMC6453885/ /pubmed/30962462 http://dx.doi.org/10.1038/s41598-019-42099-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tanaka, Mitsuru
Dohgu, Shinya
Komabayashi, Genki
Kiyohara, Hayato
Takata, Fuyuko
Kataoka, Yasufumi
Nirasawa, Takashi
Maebuchi, Motohiro
Matsui, Toshiro
Brain-transportable dipeptides across the blood-brain barrier in mice
title Brain-transportable dipeptides across the blood-brain barrier in mice
title_full Brain-transportable dipeptides across the blood-brain barrier in mice
title_fullStr Brain-transportable dipeptides across the blood-brain barrier in mice
title_full_unstemmed Brain-transportable dipeptides across the blood-brain barrier in mice
title_short Brain-transportable dipeptides across the blood-brain barrier in mice
title_sort brain-transportable dipeptides across the blood-brain barrier in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453885/
https://www.ncbi.nlm.nih.gov/pubmed/30962462
http://dx.doi.org/10.1038/s41598-019-42099-9
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