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Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells
Published on: September 24, 2017
Brain-transportable dipeptides across the blood-brain barrier in mice
Mitsuru Tanaka1, Shinya Dohgu2, Genki Komabayashi1
1Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Abstract:
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 Ki 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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