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However, the role of TKIs, including imatinib, in development of anxiety remains unclear. The prefrontal cortex (PFC) is closely associated with anxiety-like behaviors, and its metabolic components, particularly lipid- and myelin-related metabolites, are involved in their regulation. Whether imatinib affects brain metabolism remains unknown. This study aimed to evaluate the effects of imatinib on anxiety-like behaviors and to investigate associated metabolic alterations in the PFC.Methods:Anxiety-like behaviors were assessed using a battery of behavioral assays in imatinib-treated mice. PFC tissues from imatinib-treated and control mice were subjected to untargeted metabolomic analysis.Results:Imatinib-treated mice exhibited selective alterations in anxiety-like behaviors. Metabolomic analysis revealed distinct metabolic profiles between the two groups, with significant changes in lipid-related pathways, particularly sphingolipid metabolism. These findings extend the current understanding of the metabolic basis of anxiety-like behaviors and suggest that TKI treatment may influence neuropsychiatric processes through metabolic remodeling of the PFC.Conclusions:This study highlights a potential link between TKI therapy and brain metabolism and provides a framework for understanding the neurobiological basis of anxiety-related effects. These findings may inform future research on the neuropsychiatric consequences of targeted cancer therapies.<\/jats:p>","DOI":"10.31083\/ap51694","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:23:51Z","timestamp":1788438231000},"source":"Crossref","is-referenced-by-count":0,"title":["Imatinib-Induced Changes in Anxiety-Like Behaviors are Associated With Prefrontal Cortical Metabolic Remodeling in Mice"],"prefix":"10.31083","volume":"27","author":[{"given":"Jieyu","family":"Ji","sequence":"first","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanglan","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"},{"name":"School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\u2019s University, 47500 Subang Jaya, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6398-4268","authenticated-orcid":true,"given":"Zhiting","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Medicine, Dali University, 671003 Dali, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Abuelgasim KA, Ahmed GY, Alqahtani JA, Alayed AM, Alaskar AS, Malik MA. 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