Tocilizumab's effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer's model

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dc.authoridŞALVA, EMINE/0000-0002-1159-5850
dc.authoridSalva, Emine/0000-0002-1159-5850
dc.authoridAlan, Saadet/0000-0003-2329-151X
dc.authorwosidŞALVA, EMINE/CAH-3062-2022
dc.authorwosidSalva, Emine/ABI-2766-2020
dc.authorwosidAlan, Saadet/ABH-4282-2020
dc.contributor.authorElcioglu, H. Kubra
dc.contributor.authorAslan, Ersin
dc.contributor.authorAhmad, Sarfraz
dc.contributor.authorAlan, Saadet
dc.contributor.authorSalva, Emine
dc.contributor.authorElcioglu, O. Haluk
dc.contributor.authorKabasakal, Levent
dc.date.accessioned2024-08-04T20:42:33Z
dc.date.available2024-08-04T20:42:33Z
dc.date.issued2016
dc.departmentİnönü Üniversitesien_US
dc.description.abstractNeuroinflammation plays pivotal roles in the pathogenesis of Alzheimer's disease (AD). IL-6 is pleiotropic cytokine which plays significant pathological role in inflammatory diseases and causes prolonged inflammation. Additionally, IL-6 activates microglia cells and enhances the accumulation of amyloid-beta peptides. Moreover, IL-6 signal transduction is mediated by membrane-bound and soluble IL-6 receptors. Tocilizumab which is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody binds to both of these receptors and inhibits IL-6 signaling by this route. The objective was to investigate tocilizumab's potential effects in the treatment of AD. Male Sprague-Dawley rats were divided into three groups: sham (control), streptozotocin (STZ), and tocilizumab-STZ. We used a single dose of intracerebroventricular (ICV) tocilizumab, beginning 1 h prior to injection of STZ for 3 weeks. The rats in STZ and tocilizumab-STZ groups were given ICV-STZ (3 mg/kg). Behavioral parameters were evaluated on days 17-20 and the rats were sacrificed on day-21 to examine histopathological changes. STZ injection caused significant decrease in the mean escape latency in passive avoidance and also declined the performance improvement in Morris water maze tests. Tocilizumab-STZ group significantly improved learning and spatial memory functions by increasing RLT in the passive avoidance and by shortening escape latency in reaching the platform in the Morris water maze. Histopathological changes were examined using hematoxylin and eosin and immunohistochemical (IHC) stainings. IHC analysis revealed that while protein expressions of amyloid- (3.5 +/- A 0.2) and IL-6 (2.9 +/- A 0.4) showed intense immune-positivity in STZ group, amyloid- (1.3 +/- A 0.1) and IL-6 (1.5 +/- A 0.2) immunoreactivities were substantially decreased in tocilizumab treatment group. We conclude that tocilizumab treatment attenuated significantly STZ-induced cognitive impairment and histopathological changes. Further studies would be desirable to investigate clinically relevant protective effects of tocilizumab in AD.en_US
dc.description.sponsorshipMarmara University Scientific Research Community [SAG-C-YLP-120613-0241]en_US
dc.description.sponsorshipThis research work was supported by the Marmara University Scientific Research Community (Project No: SAG-C-YLP-120613-0241).en_US
dc.identifier.doi10.1007/s11010-016-2762-6
dc.identifier.endpage28en_US
dc.identifier.issn0300-8177
dc.identifier.issn1573-4919
dc.identifier.issue1-2en_US
dc.identifier.pmid27443846en_US
dc.identifier.scopus2-s2.0-84979243126en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage21en_US
dc.identifier.urihttps://doi.org/10.1007/s11010-016-2762-6
dc.identifier.urihttps://hdl.handle.net/11616/97439
dc.identifier.volume420en_US
dc.identifier.wosWOS:000382112200003en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofMolecular and Cellular Biochemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectTocilizumaben_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectIntracerebroventricularen_US
dc.subjectStreptozotocinen_US
dc.subjectInflammationen_US
dc.subjectMemoryen_US
dc.titleTocilizumab's effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer's modelen_US
dc.typeArticleen_US

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