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However, the cognitive effects of different intensities of exercise and its underlying mechanisms are not fully understood. The aim of this paper was to investigate the effects of different intensities of treadmill exercise on cognition in rats from the perspective of metabolomic analysis. In this study, ninety-six male rats were randomly divided into four groups: control group (CON group, <jats:italic>n<\/jats:italic>\u2009=\u200924), low-intensity running group (LIR group, <jats:italic>n<\/jats:italic>\u2009=\u200924), medium-intensity running group (MIR group, <jats:italic>n<\/jats:italic>\u2009=\u200924), and high-intensity running group (HIR group, <jats:italic>n<\/jats:italic>\u2009=\u200924). After 4 weeks of treadmill running, rats in the LIR group located the platform significantly faster than those in the CON(<jats:italic>p<\/jats:italic>\u2009=\u20090.027) and HIR(<jats:italic>p<\/jats:italic>\u2009=\u20090.011) groups. After 8 weeks of treadmill running, rats in the LIR and MIR groups also found the platform more quickly than those in CON group (<jats:italic>p<\/jats:italic>\u2009=\u20090.003 and <jats:italic>p<\/jats:italic>\u2009=\u20090.015, respectively). Additionally, rats in the MIR group showed significantly increased superoxide dismutase (SOD)\/catalase (CAT) in the hippocampus compared with those exposed to HIR(<jats:italic>p<\/jats:italic>\u2009=\u20090.03), LIR(<jats:italic>p<\/jats:italic>\u2009=\u20090.0008), and CON(<jats:italic>p<\/jats:italic>\u2009=\u20090.0004). Metabolomic analysis revealed that, after 8 weeks of running, 14 metabolites with similar characteristics differed between the MIR and HIR groups compared to the CON group. The LIR group showed significant alterations in 12 key metabolites compared to the CON group. The LIR, MIR, and HIR groups also demonstrated significant changes in 3, 4, and 3 metabolic pathways respectively, when compared to the CON group. In conclusion, the above results indicate that LIR can effectively decrease fumarate accumulation, thereby enhancing the TCA cycle and brain energy metabolism which in turn improved cognitive function, while MIR can modify glutathione metabolism to alleviate oxidative stress (OS), supporting cognitive function.<\/jats:p>","DOI":"10.1007\/s13105-025-01094-7","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T01:30:32Z","timestamp":1748050232000},"page":"687-697","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nuclear magnetic resonance-based metabolomic study of rat brain after different intensity treadmill running"],"prefix":"10.1007","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-8974","authenticated-orcid":false,"given":"Ni","family":"Zeng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Juan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Peng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-8155","authenticated-orcid":false,"given":"Guo-Xin","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"issue":"6","key":"1094_CR1","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1152\/physiol.00017.2017","volume":"32","author":"C Vivar","year":"2017","unstructured":"Vivar C, van Praag H (2017) Running changes the brain: the long and the short of it. 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