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A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration.

ABSTRACT: The transport and accumulation of orally administered functional food-derived peptides in the brain was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administration. Stable isotope-labeled Tyr-Pro (Tyr-[¹³C₅,¹⁵N]Pro) was orally administered to male ICR mice at 10 or 100 mg/kg. Surprisingly, the intact labeled Tyr-Pro exhibited maximal plasma and brain levels 15 min after administration (plasma: area under the curve [AUC_0-120 min], 1331 ± 267 pmol·min/mL-plasma; brain: AUC_0-120 min of 0.34 ± 0.11 pmol·min/mg-dry brain, at 10 mg/kg). In addition, we detected labeled Tyr-Pro in the brain parenchyma, indicating a validated blood-brain-barrier (BBB) transportability. Moreover, we confirmed the preferable accumulation of Tyr-Pro in the hypothalamus, hippocampus, and cortex with > 0.02 pmol/mg-tissue. In conclusion, we provided the first evidence that orally administered Tyr-Pro at 10 mg/kg directly entered the blood circulation with an absorption ratio of 0.15%, of which 2.5% of Tyr-Pro was transported from the plasma to the mouse brain parenchyma.

SUBMITTER: Cheng L

PROVIDER: S-EPMC10560274 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration.

Cheng Lihong L Tanaka Mitsuru M Yoshino Atsuko A Nagasato Yuki Y Takata Fuyuko F Dohgu Shinya S Matsui Toshiro T

Scientific reports 20231007 1

The transport and accumulation of orally administered functional food-derived peptides in the brain was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administration. Stable isotope-labeled Tyr-Pro (Tyr-[13C5,15N]Pro) was orally administered to male ICR mice at 10 or 100 mg/kg. Surprisingly, the intact labeled Tyr-Pro exhibited maximal ...[more]

PMID: 37805661

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Project description:Maternal antibiotics administration (MAA) is among the widely used therapeutic approaches in pregnancy. Although published evidence demonstrates that infants exposed to antibiotics immediately after birth have altered recognition memory responses at one month of age, very little is known about in utero effects of antibiotics on the neuronal function and behavior of children after birth. Therefore, this study aimed to evaluate the impact of MAA at different periods of pregnancy on memory decline and brain structural alterations in young mouse offspring after their first month of life. To study the effects of MAA on 4-week-old offspring, pregnant C57BL/6J mouse dams (2-3-month-old; n = 4/group) were exposed to a cocktail of amoxicillin (205 mg/kg/day) and azithromycin (51 mg/kg/day) in sterile drinking water (daily/1 week) during either the 2nd or 3rd week of pregnancy and stopped after delivery. A control group of pregnant dams was exposed to sterile drinking water alone during all three weeks of pregnancy. Then, the 4-week-old offspring mice were first evaluated for behavioral changes. Using the Morris water maze assay, we revealed that exposure of pregnant mice to antibiotics at the 2nd and 3rd weeks of pregnancy significantly altered spatial reference memory and learning skills in their offspring compared to those delivered from the control group of dams. In contrast, no significant difference in long-term associative memory was detected between offspring groups using the novel object recognition test. Then, we histologically evaluated brain samples from the same offspring individuals using conventional immunofluorescence and electron microscopy assays. To our knowledge, we observed a reduction in the density of the hippocampal CA1 pyramidal neurons and hypomyelination in the corpus callosum in groups of mice in utero exposed to antibiotics at the 2nd and 3rd weeks of gestation. In addition, offspring exposed to antibiotics at the 2nd or 3rd week of gestation demonstrated a decreased astrocyte cell surface area and astrocyte territories or depletion of neurogenesis in the dentate gyrus and hippocampal synaptic loss, respectively. Altogether, this study shows that MAA at different times of pregnancy can pathologically alter cognitive behavior and brain development in offspring at an early age after weaning.

Dataset Information

A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration.

Publications

A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration.

Similar Datasets

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