{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:13:22Z","timestamp":1788894802801,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"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 Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methotrexate (MTX) is an antineoplastic agent and has neurotoxic effects. It exerts its toxic effect on the brain by triggering inflammation and apoptosis. Cannabidiol (CBD) is an agent known for its antioxidant, anti\u2010inflammatory effects in various tissues. The aim of this study is to examine the protective effects of CBD treatment in various brain structures from MTX damage and to evaluate the effect of intracellular pathways involved in apoptosis. Thirty\u2010two adult Wistar Albino female rats were divided into four groups as control, MTX (20\u2009mg\/kg intraperitoneally [i.p.]), MTX\u2009+\u2009CBD (0.1\u2009mL of 5\u2009mg\/kg i.p.), and CBD (for 7 days, i.p.). At the end of the experiment, brain tissues collected for biochemical analyses as total oxidant status (TOS), total antioxidant status, oxidative stress index (OSI), histopathological and immunohistochemical analyses as tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), serotonin, mammalian target of rapamycin (mTOR) staining, genetic analyses as caspase\u20109 (Cas\u20109), caspase\u201012 (Cas\u201012), C\/EBP homologous protein (CHOP), and cytochrome\u2010c (Cyt\u2010c) gene expressions. In the histopathological and immunohistochemical evaluation, hyperemia, microhemorrhage, neuronal loss, and significant decreasing expressions of seratonin were observed in the cortex, hippocampus, and cerebellum regions in the MTX group. mTOR, TNF\u2010\u03b1, Cas\u20109, Cas\u201012, CHOP, and Cyt\u2010c expressions with TOS and OSI levels were increased in the cortex. It was observed that these findings were reversed after CBD application in all regions. MTX triggers neuronal apoptosis via endoplasmic reticulum and mitochondrial stress while destroying serotonergic neurons. The reversal of the pathological changes with CBD treatment proves that it has anti\u2010inflammatory and antiapoptotic activity in brain.<\/jats:p>","DOI":"10.1002\/jbt.23571","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T02:55:30Z","timestamp":1699239330000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The ameliorative effects of cannabidiol on methotrexate\u2010induced neuroinflammation and neuronal apoptosis via inhibiting endoplasmic reticulum and mitochondrial stress"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-044X","authenticated-orcid":false,"given":"Melike D.","family":"Unlu","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine Suleyman Demirel University  Isparta 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