{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:53:42Z","timestamp":1775073222739,"version":"3.50.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ingenious Ingredients L.P."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>1-Methylxanthine (1-MX) is the major metabolite of caffeine and paraxanthine and might contribute to their activity. 1-MX is an adenosine receptor antagonist and increases the release and survivability of neurotransmitters; however, no study has addressed the potential physiological effects of 1-MX ingestion. The aim of this study was to compare the effect of 1-MX on memory and related biomarkers in rats compared to control. Memory (escape latency in the Morris water maze test), neurotransmitters (acetylcholine, dopamine, gamma-amino butyric acid (GABA)), and neurochemicals (BDNF, catalase, glutathione, Amyloid Beta and cyclic GMP) were analyzed from whole brain samples in young (8-weeks-old) and aged (16-months-old) rats following 12 days of supplementation (100 mg\/d HED of 1-MX [UPLEVEL\u00ae, Ingenious Ingredients L.P., Lewisville, TX, USA]) via oral gavage. 1-MX supplementation reduced escape latency by 39% in young animals and 27% in aged animals compared to controls (both <jats:italic>p<\/jats:italic>&lt;0.001). Additionally, 1-MX increased the levels of acetylcholine, dopamine, GABA, and cyclic GMP (all <jats:italic>p<\/jats:italic>&lt;0.001). Furthermore, 1-MX supplementation led to reduced amyloid beta and higher catalase, BDNF and glutathione concentrations (<jats:italic>p<\/jats:italic>&lt;0.001). Collectively, our findings suggest that 1-MX may have cognitive-enhancing and neuroprotective properties.<\/jats:p>","DOI":"10.1371\/journal.pone.0313486","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:48:17Z","timestamp":1737053297000},"page":"e0313486","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["1-Methylxanthine enhances memory and neurotransmitter levels"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7345-9635","authenticated-orcid":true,"given":"Ralf","family":"J\u00e4ger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidney","family":"Abou Sawan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Orr\u00fa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0230-6586","authenticated-orcid":true,"given":"Grant M.","family":"Tinlsey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Purpura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn D.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok","family":"Godavarthi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"issue":"12","key":"pone.0313486.ref001","doi-asserted-by":"crossref","first-page":"e149371","DOI":"10.1172\/JCI149371","article-title":"Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription","volume":"132","author":"I Paiva","year":"2022","journal-title":"J Clin Invest"},{"key":"pone.0313486.ref002","doi-asserted-by":"crossref","first-page":"1176382","DOI":"10.3389\/fnbeh.2023.1176382","article-title":"Coffee consumption decreases the connectivity of the posterior Default Mode Network (DMN) at rest","volume":"17","author":"M Pic\u00f3-P\u00e9rez","year":"2023","journal-title":"Front. 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