Chronic pantoprazole exposure induces behavioral deficits and region‑specific molecular changes in the rat motor cortex and cerebellum

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dc.authorid0009-0005-3028-5371
dc.authorid0000-0002-9462-0862
dc.authorid0000-0001-7094-3336
dc.contributor.authorÇaglar, Emine
dc.contributor.authorElibol, Birsen
dc.contributor.authorPolat, Nurhayat
dc.contributor.authorDursun, İlknur
dc.date.accessioned2026-07-13T10:16:22Z
dc.date.available2026-07-13T10:16:22Z
dc.date.issued2026
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractProton pump inhibitors are widely used, but their long‑term effects on the central nervous system are not well understood. In this study, we investigated whether chronic pantoprazole use alters sensorimotor function, oxidative stress, inflammatory response, and apoptosis in the motor cortex and cerebellum. Twenty‑one female Wistar rats were randomized to control (C), gavage control (GC), or pantoprazole (P; 20 mg/kg/day for 12 weeks) groups. Sensorimotor coordination (rotarod), water‑maze swim velocity, and open‑field locomotion were assessed as behavioral parameters. The cortical and cerebellar tissues were analyzed by Enzyme‑Linked Immunosorbent Assay (ELISA) for apoptosis, inflammation, and oxidative stress. Pantoprazole impaired sensorimotor coordination compared to both control groups. However, its effects on swim velocity and locomotor activity were primarily significant when compared to the naive control group, suggesting that gavage‑related stress may have contributed to these behavioral outcomes. Bcl‑2‑associated X protein (BAX) and Bcl‑2 associated agonist of cell death (BAD) protein levels and the BAX/Bcl‑2 ratio increased with pantoprazole, particularly in the motor cortex, indicating enhanced pro‑apoptotic activity. While tumor necrosis factor levels did not change, interleukin (IL)‑6 and IL‑1β levels were significantly higher in the cerebellum, suggesting neuroinflammatory activation associated with both pantoprazole and gavage‑induced stress. Furthermore, oxidative stress analyses revealed elevated malondialdehyde and oxidative stress index levels, as well as increased total antioxidant status, in specific regions, suggesting an imbalance between oxidative and antioxidant responses. Chronic pantoprazole administration resulted in modest motor deficits and region‑specific molecular alterations, including a pro‑apoptotic shift in the motor cortex. In addition, an inflammatory/compensatory antioxidant response in the cerebellum was observed due to both gavage‑induced stress and pantoprazole administration. These findings highlight the need for further studies on dose‑response, reversibility, and synaptic consequences, and suggest the importance of considering the risks of prolonged proton pump inhibitors exposure.
dc.description.sponsorshipThis work is part of a research project funded by the Istinye University Research Council (Grant number: 2024‑8‑1). Bu çalışma, İstinye Üniversitesi Araştırma Konseyi tarafından finanse edilen bir araştırma projesinin (Proje numarası: 2024-8-1) bir parçasıdır.
dc.identifier.citationÇaglar, E., Elibol, B., Polat, N., & Dursun, İ. (2026). Chronic pantoprazole exposure induces behavioral deficits and region‑specific molecular changes in the rat motor cortex and cerebellum. Acta Neurobiologiae Experimentalis, 86(2), pp. 127-138. https://doi.org/10.55782/4sbep348
dc.identifier.doi10.55782/4sbep348
dc.identifier.endpage138
dc.identifier.issn0065-1400
dc.identifier.issn1689-0035
dc.identifier.issue2
dc.identifier.pmidPMID: 42370619
dc.identifier.scopus2-s2.0-105044230830
dc.identifier.scopusqualityQ3
dc.identifier.startpage127
dc.identifier.urihttps://doi.org/10.55782/4sbep348
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1534
dc.identifier.volume86
dc.identifier.wosWOS:001822106500006
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorDursun, İlknur
dc.institutionauthorid0000-0001-7094-3336
dc.language.isoen
dc.publisherNencki Institute of Experimental Biology
dc.relation.ispartofActa Neurobiologiae Experimentalis
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectPantoprazole
dc.subjectCerebellum
dc.subjectMotor Cortex
dc.subjectSensorimotor Coordination
dc.titleChronic pantoprazole exposure induces behavioral deficits and region‑specific molecular changes in the rat motor cortex and cerebellum
dc.typeArticle
dspace.entity.typePublication

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