Branched-chain amino acids govern the high learning ability phenotype in tokai high avoider (THA) rats
Open accessAbstract
To fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required. THA rats established by crossing those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.
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Evidence suggests that branched-chain amino acid modulation may be useful in cognition disorders.
“Although exploratory studies remain in their infancy, evidence suggests that BCAA modulation may be useful in cognition disorders (339–341).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [339]
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Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
- Authors
- Shida, Y., Endo, H., Owada, S., Inagaki, Y., Sumiyoshi, H., Kamiya, A., Eto, T., & Tatemichi, M.
- Affiliations
- Tokai University (JP)
- Central Institute for Experimental Animals (JP)
- Corresponding author
- Endo, Hitoshi
- Venue
- Scientific Reports
- Published
- 2021-11-29
- Volume
- 11
- Issue
- 1
- Pages
- 23104-23104
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8630195
- OpenAlex
- W3215860990
- Cited by
- 6
- References
- 79
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. (15K12728, 18K10058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- branched-chain amino acids, learning ability, hippocampus, branched-chain amino acid metabolism, acetylcholine synthesis, acetyl-CoA, interindividual variability, learning and memory, dementia prevention, learning disabilities
- MeSH terms
- Amino Acids, Branched-Chain, Animals, Animal Feed, Behavior, Behavior, Animal, Diet, Hippocampus, Learning, Liver, Male, Memory, Phenotype, Psychophysics, Rats, Wistar, Models, Animal, Rats, Metabolome
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