Vortioxetine ameliorates motor and cognitive impairments in the rotenone-induced Parkinson's disease via targeting TLR-2 mediated neuroinflammation

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dc.authorid0000-0002-0660-971X
dc.authorid0000-0001-8186-4852
dc.authorid0000-0002-3616-0052
dc.authorid0000-0003-3418-8825
dc.authorid0000-0001-8874-2241
dc.authorid0000-0003-2630-6182
dc.contributor.authorSamur, Dilara Nemutlu
dc.contributor.authorAkcay, Guven
dc.contributor.authorYildirim, Sendegul
dc.contributor.authorOzkan, Ayse
dc.contributor.authorCeker, Tugce
dc.contributor.authorDerin, Narin
dc.contributor.authorTanriover, Gamze
dc.date.accessioned2026-01-24T12:31:16Z
dc.date.available2026-01-24T12:31:16Z
dc.date.issued2022
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractParkinson's disease (PD) is characterized by motor and non-motor symptoms associated with dopaminergic and non-dopaminergic injury. Vortioxetine is a multimodal serotonergic antidepressant with potential procognitive effects. This study aimed to explore the effects of vortioxetine on motor functions, spatial learning and memory, and depression-like behavior in the rotenone-induced rat model of PD. Male Sprague-Dawley rats were daily administered with the rotenone (2 mg kg(-1), s.c.) and/or vortioxetine (10 mg kg(-1), s.c.) for 28 days. Motor functions (rotarod, catalepsy, open-field), depression-like behaviors (sucrose preference test), anxiety (elevated plus maze), and spatial learning and memory abilities (novel object recognition and Morris water maze) were evaluated in behavioral tests. Then immunohistochemical, neurochemical, and biochemical analysis on specific brain areas were performed. Vortioxetine treatment markedly reduced rotenone-induced neurodegeneration, improved motor and cognitive dysfunction, decreased depression-like behaviors without affecting anxiety-like parameters. Vortioxetine also restored the impaired inflammatory response and affected neurotransmitter levels in brain tissues. Interestingly, vortioxetine was thought to trigger a sort of dysfunction in basal ganglia as evidenced by increased Toll-like receptor-2 (TLR-2) and decreased TH immunoreactivity only in substantia nigra tissue of PD rats compared to the control group. The present study indicates that vortioxetine has beneficial effects on motor dysfunction as well as cognitive impairment associated with neurodegeneration in the rotenone-induced PD model. Possible mechanisms underlying these beneficial effects cover TLR-2 inhibition and neuro -chemical restoration of vortioxetine.
dc.description.sponsorshipScientific and Technological Research Council of Turkey, TUBITAK [219S253]; Akdeniz University Research Foundation [TDK-2019-4412]
dc.description.sponsorshipThis work was supported by grants from the Scientific and Techno-logical Research Council of Turkey, TUBITAK (219S253) and Akdeniz University Research Foundation (TDK-2019-4412) . We are grateful to Devrim Demir Dora for her valuable technical and human support. We also thank to Lundbeck A/S for their kindly providing the vortioxetine.
dc.identifier.doi10.1016/j.neuropharm.2022.108977
dc.identifier.issn0028-3908
dc.identifier.issn1873-7064
dc.identifier.pmid35092748
dc.identifier.urihttps://doi.org/10.1016/j.neuropharm.2022.108977
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5766
dc.identifier.volume208
dc.identifier.wosWOS:000785008600001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofNeuropharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectParkinsons disease
dc.subjectToll-like receptors
dc.subjectNeurodegeneration
dc.subjectVortioxetine
dc.titleVortioxetine ameliorates motor and cognitive impairments in the rotenone-induced Parkinson's disease via targeting TLR-2 mediated neuroinflammation
dc.typeArticle

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