{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:36:53Z","timestamp":1773661013977,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["16H05107"],"award-info":[{"award-number":["16H05107"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["16K15194"],"award-info":[{"award-number":["16K15194"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["19K16359"],"award-info":[{"award-number":["19K16359"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["17K08287"],"award-info":[{"award-number":["17K08287"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grants-in-Aid for Young Scientists of Showa Pharmaceutical University","award":["H30-2"],"award-info":[{"award-number":["H30-2"]}]},{"name":"Grants-in-Aid for Young Scientists of Showa Pharmaceutical University","award":["R3-2"],"award-info":[{"award-number":["R3-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1\u00d7) or a diet containing 16 graded Met doses (1.2\u00d7\u201313\u00d7). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 \u00b5M) on the 12\u00d7Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10\u00d7Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10\u00d7Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning\/memory activity in a Y-maze test, which were reflections of negative\/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.<\/jats:p>","DOI":"10.3390\/ijms23020928","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A High-Methionine Diet for One-Week Induces a High Accumulation of Methionine in the Cerebrospinal Fluid and Confers Bipolar Disorder-like Behavior in Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-205X","authenticated-orcid":false,"given":"Isao","family":"Ishii","sequence":"first","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"},{"name":"Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"},{"name":"Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Shimonaga","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maika","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Tsushima","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asumi","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Tosaka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waka","family":"Kamichatani","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Akahoshi","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1021\/jf60191a036","article-title":"Toxicities of methionine and other amino acids","volume":"22","author":"Benevenga","year":"1974","journal-title":"J. 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