{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:52:20Z","timestamp":1790913140914,"version":"4.1.0"},"reference-count":110,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Methotrexate (MTX) is a cytotoxic drug that can trigger neurotoxicity via enhancing oxidative stress, apoptosis, and inflammation. On the other hand, erythropoietin (EPO) functions as an antioxidant, anti-apoptotic, and anti-inflammatory agent, in addition to its hematopoietic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>The present study was developed to examine the neuroprotective impact of EPO against MTX-provoked neurotoxicity in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Chemo fog was elicited in Wistar rats via injection of one dosage of MTX (20\u2009mg\/kg, i.p) on the sixth day of the study. EPO was injected at 500\u2009IU\/kg\/day, i.p for 10 successive days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>MTX triggered memory and learning impairment as evidenced by Morris water maze, passive avoidance, and Y-maze cognitive tests. In addition, MTX induced oxidative stress as evident from the decline in hippocampal Nrf2 and HO-1 levels. MTX brought about apoptosis, as demonstrated by the elevation in p53, caspase-3, and Bax levels, as well as the decrease in Bcl2 levels. MTX also decreased Beclin-1, an autophagy-related marker, and increased P62 expression. In addition, MTX downregulated Sirt-1\/AKT\/FoxO3a pathway and increased miRNA-34a gene expression. Moreover, MTX increased acetylcholinesterase activity and reduced neurogenesis. EPO administration remarkably counteracted MTX-induced molecular and behavioral disorders in rat hippocampi.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our findings impart preclinical indication for repurposing of EPO as a promising neuroprotective agent through modulating miRNA-34a, autophagy, and the Sirt-1\/FoxO3a signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811241295379","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T08:35:37Z","timestamp":1731486937000},"page":"147-163","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Repurposing of erythropoietin as a neuroprotective agent against methotrexate-induced neurotoxicity in rats"],"prefix":"10.1177","volume":"39","author":[{"given":"Nadine 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