Next Article in Journal
Vitamin D Supplementation and Physical Activity of Young Soccer Players during High-Intensity Training
Next Article in Special Issue
Palatability of Goat’s versus Cow’s Milk: Insights from the Analysis of Eating Behavior and Gene Expression in the Appetite-Relevant Brain Circuit in Laboratory Animal Models
Previous Article in Journal
Dietary Fiber Intake (Supplemental or Dietary Pattern Rich in Fiber) and Diabetic Kidney Disease: A Systematic Review of Clinical Trials
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle

Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System

Research Laboratories for Health Science & Food Technologies, Kirin Company Ltd, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan
Division of Pharmacology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
AMED-CREST, Chiyoda-ku 100-0004, Tokyo, Japan
Author to whom correspondence should be addressed.
Nutrients 2019, 11(2), 348;
Received: 10 January 2019 / Revised: 2 February 2019 / Accepted: 3 February 2019 / Published: 6 February 2019
(This article belongs to the Special Issue Nutrition and Central Nervous System)
PDF [1335 KB, uploaded 21 February 2019]


Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of the WY dipeptide on memory impairment to elucidate the mechanisms. Here, we showed that oral administration of dipeptides of WY, tryptophan-methionine (WM), tryptophan-valine, tryptophan-leucine, and tryptophan-phenylalanine improved spontaneous alternation of the Y-maze test in scopolamine-induced amnesic mice. In contrast, tyrosine-tryptophan, methionine-tryptophan, tryptophan, tyrosine, and methionine had no effect. These results indicated that the conformation of dipeptides with N-terminal tryptophan is required for their memory improving effects. WY dipeptide inhibited the monoamine oxidase B activity in vitro and increased dopamine levels in the hippocampus and frontal cortex, whereas tryptophan did not cause these effects. In addition, the treatment with SCH-23390, a dopamine D1-like receptor antagonist, and the knockdown of the hippocampal dopamine D1 receptor partially attenuated the memory improvement induced by the WY dipeptide. Importantly, WY dipeptide improved the spontaneous alternations of the Y-maze test in aged mice. These results suggest that the WY dipeptide restores memory impairments by augmenting dopaminergic activity. The development of supplements rich in these peptides might help to prevent age-related cognitive decline. View Full-Text
Keywords: dipeptide; dopamine; hippocampus; memory; monoamine oxidase B dipeptide; dopamine; hippocampus; memory; monoamine oxidase B

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Ano, Y.; Ayabe, T.; Ohya, R.; Kondo, K.; Kitaoka, S.; Furuyashiki, T. Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System. Nutrients 2019, 11, 348.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top