Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats

Abstract 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 fact...

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Autores principales:	Yukari Shida, Hitoshi Endo, Satoshi Owada, Yutaka Inagaki, Hideaki Sumiyoshi, Akihide Kamiya, Tomoo Eto, Masayuki Tatemichi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04d3a897d1c547f89053a9dd7953d361
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spelling	oai:doaj.org-article:04d3a897d1c547f89053a9dd7953d3612021-12-05T12:14:12ZBranched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats10.1038/s41598-021-02591-72045-2322https://doaj.org/article/04d3a897d1c547f89053a9dd7953d3612021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02591-7https://doaj.org/toc/2045-2322Abstract 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.Yukari ShidaHitoshi EndoSatoshi OwadaYutaka InagakiHideaki SumiyoshiAkihide KamiyaTomoo EtoMasayuki TatemichiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yukari Shida Hitoshi Endo Satoshi Owada Yutaka Inagaki Hideaki Sumiyoshi Akihide Kamiya Tomoo Eto Masayuki Tatemichi Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats
description	Abstract 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.
format	article
author	Yukari Shida Hitoshi Endo Satoshi Owada Yutaka Inagaki Hideaki Sumiyoshi Akihide Kamiya Tomoo Eto Masayuki Tatemichi
author_facet	Yukari Shida Hitoshi Endo Satoshi Owada Yutaka Inagaki Hideaki Sumiyoshi Akihide Kamiya Tomoo Eto Masayuki Tatemichi
author_sort	Yukari Shida
title	Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats
title_short	Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats
title_full	Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats
title_fullStr	Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats
title_full_unstemmed	Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats
title_sort	branched-chain amino acids govern the high learning ability phenotype in tokai high avoider (tha) rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/04d3a897d1c547f89053a9dd7953d361
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Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats

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