Summary: Tyr-Pro, a brain-transportable dipeptide derived from soy protein, improved both short-term and long-term memory in mouse models used to simulate Alzheimer’s disease.
Source: Kyushu University
Overview
Researchers at Kyushu University in Japan report that a small protein fragment produced from soybean proteins can reach the brain after oral ingestion and reduce memory loss in mice treated to mimic Alzheimer’s disease. The molecule, a dipeptide named Tyr-Pro because it is composed of the amino acids tyrosine (Tyr) and proline (Pro), is notable for remaining intact through digestion and crossing the blood–brain barrier to exert effects on neural function.
Many peptides are broken down in the digestive tract or fail to pass the highly selective blood–brain barrier, limiting their potential as orally delivered neuroactive agents. According to Toshiro Matsui, professor in the Faculty of Agriculture at Kyushu University and lead author of the study published in npj Science of Food, previous work by the team first identified a dipeptide capable of making this journey. The current study goes further by testing whether that dipeptide can alter behavior in an established mouse model of memory impairment.
Study design and methods
In collaboration with researchers at Fukuoka University, the team administered Tyr-Pro orally to mice for several days before and after inducing memory impairment using a commonly applied fragment of amyloid β peptide (amyloid β25–35), which reliably produces cognitive deficits in rodents. Memory was assessed using standard behavioral tests sensitive to short-term (working) and long-term memory decline.
Short-term memory was evaluated using a spontaneous alternation task in a simple maze, which measures a mouse’s tendency to explore different arms rather than repeat the same path. Long-term memory was assessed with a passive avoidance task, in which mice learn to avoid a dark compartment where they previously received a mild aversive stimulus; latency to enter the area measures retention of that training.
Key findings
Mice treated with Tyr-Pro showed measurable protection against amyloid β-induced memory deficits. In the short-term memory test, impaired mice that had received the dipeptide over a two-week period performed better than impaired mice that did not receive Tyr-Pro, although both groups were still outperformed by healthy control mice without induced impairment. A similar pattern emerged in the long-term memory test: mice given Tyr-Pro demonstrated longer avoidance latency compared with untreated, impaired animals, indicating improved retention.
Importantly, this study provides in vivo evidence that an orally administered soy-derived dipeptide can be transported across the blood–brain barrier and produce behavioral improvements in a model of Alzheimer’s-like memory impairment. While prior reports have suggested some peptides might slow cognitive decline, this is the first study to combine behavioral benefit with evidence that the molecule reaches the brain intact.
Implications and next steps
The findings raise the possibility that diet-derived small peptides or functional foods could one day contribute to strategies for preventing or reducing memory decline. Matsui cautions that further research is required to determine whether these benefits translate to humans, to clarify the mechanisms by which Tyr-Pro influences neural processes, and to establish appropriate dosing and safety. Nevertheless, the study represents an important step toward understanding how specific food components interact with the brain and affect cognition.
About this neuroscience research article
Source:
Kyushu University
Media Contacts:
William J. Potscavage Jr. – Kyushu University
Image Source:
The image is credited to William J. Potscavage Jr., Kyushu University.
Original Research: Open access
“Brain-transportable soy dipeptide, Tyr-Pro, attenuates amyloid β peptide25-35-induced memory impairment in mice” by Mitsuru Tanaka, Hayato Kiyohara, Atsuko Yoshino, Akihiro Nakano, Fuyuko Takata, Shinya Dohgu, Yasufumi Kataoka & Toshiro Matsui. npj Science of Food. DOI: 10.1038/s41538-020-0067-3
Abstract (summary)
The researchers performed in vivo experiments using amyloid β25–35-induced mice to evaluate the potential of the blood–brain barrier transportable soy dipeptide Tyr-Pro to combat memory impairment. Oral administration of Tyr-Pro (100 mg/kg, twice daily) for 16 days significantly improved impaired memory in measures of spontaneous alternation and increased step-through latency in amyloid β-treated mice.