{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:30:18Z","timestamp":1778088618979,"version":"3.51.4"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Chemotherapy\u2010induced peripheral neurotoxicity (CIPN) is one of the most common dose\u2010limiting side effects of paclitaxel (PTX) treatment. Many age\u2010related changes have been hypothesized to underlie susceptibility to damage or impaired regeneration\/repair after nerve injury. The results of these studies, however, are inconclusive and other potential biomarkers of nerve impairment need to be investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010four young (2\u2009months) and 24 adult (9\u2009months) Wistar male rats were randomized to either PTX treatment (10\u2009mg\/kg i.v. once\/week for 4\u2009weeks) or vehicle administration. Neurophysiological and behavioral tests were performed at baseline, after 4\u2009weeks of treatment and 2\u2010week follow\u2010up. Skin biopsies and nerve specimens collected from sacrificed animals were examined for intraepidermal nerve fiber (IENF) density assessment and nerve morphology\/morphometry. Blood and liver samples were collected for targeted metabolomics analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the end of treatment, the neurophysiological studies revealed a reduction in sensory nerve action potential amplitude (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) in the caudal nerve of young PTX\u2010animals, and in both the digital and caudal nerve of adult PTX\u2010animals (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). A significant decrease in the mechanical threshold was observed only in young PTX\u2010animals (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), but not in adult PTX\u2010ones. Nevertheless, both young and adult PTX\u2010rats had reduced IENF density (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001), which persisted at the end of follow\u2010up period. Targeted metabolomics analysis showed significant differences in the plasma metabolite profiles between PTX\u2010animals developing peripheral neuropathy and age\u2010matched controls, with triglycerides, diglycerides, acylcarnitines, carnosine, long chain ceramides, sphingolipids, and bile acids playing a major role in the response to PTX administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our study identifies for the first time multiple related metabolic axes involved in PTX\u2010induced peripheral neurotoxicity, and suggests age\u2010related differences in CIPN manifestations and in the metabolic profile.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12609","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T12:03:29Z","timestamp":1703160209000},"page":"58-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of age on metabolomic 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