Research Paper Volume 11, Issue 10 pp 2949—2967
Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline
- 1 Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, the University of Tokyo, Tokyo 113-8657, Japan
- 2 Research Laboratories for Health Science & Food Technologies, Kirin Company Ltd., Yokohama-shi, Kanagawa 236-0004, Japan
- 3 Faculty of Science, Gakushuin University, Toshima-ku, Tokyo 171-8588, Japan
received: February 14, 2019 ; accepted: April 3, 2019 ; published: May 23, 2019 ;https://doi.org/10.18632/aging.101909
How to Cite
Copyright: Ano et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The rapid growth in aging populations has made prevention of age-related memory decline and dementia a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help prevent cognitive decline; furthermore, intake of Camembert cheese prevents microglial inflammation and Alzheimer’s pathology in mouse models. To elucidate the molecular mechanisms underlying the preventive effects of fermented dairy products, we screened peptides from digested milk protein for their potential to regulate the activation of microglia. We identified dipeptides of tryptophan–tyrosine (WY) and tryptophan–methionine that suppressed the microglial inflammatory response and enhanced the phagocytosis of amyloid-β (Aβ). Various fermented dairy products and food materials contain the WY peptide. Orally administered WY peptide was smoothly absorbed into blood, delivered to the brain, and improved the cognitive decline induced by lipopolysaccharide via the suppression of inflammation. Intake of the WY peptide prevented microglial inflammation, hippocampal long-term potential deficit, and memory impairment in aged mice. In an Alzheimer’s model using 5×FAD mice, intake of the WY peptide also suppressed microglial inflammation and accumulation of Aβ, which improved cognitive decline. The identified dipeptides regulating microglial activity could potentially be used to prevent cognitive decline and dementia related to inflammation.