Early stage alterations in CA1 extracellular region proteins indicate dysregulation of IL6 and iron homeostasis in the 5XFAD Alzheimer's disease mouse model

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dc.authorid0000-0002-1079-8832
dc.contributor.authorGürel, Büşra
dc.contributor.authorCansev, Mehmet
dc.contributor.authorSevinç, Cansu
dc.contributor.authorKeleştemur, Seda
dc.contributor.authorÖcalan, Büşra
dc.contributor.authorÇakır, Ayşen
dc.contributor.authorAydın, Sami
dc.contributor.authorKahveci, Nevzat
dc.contributor.authorOzansoy, Mehmet
dc.contributor.authorTaşkapılıoğlu, Özlem
dc.contributor.authorUlus, İsmail Hakkı
dc.contributor.authorKarayel Başar, Merve
dc.contributor.authorŞahin, Betül
dc.contributor.authorTüzüner, Mete Bora
dc.contributor.authorBaykal, Ahmet Tarık
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:57:18Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:57:18Z
dc.date.issued2018
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.descriptionWOS: 000423364400015
dc.descriptionPubMed ID: 29376847
dc.description.abstractIn recent years, an increasing number of research papers revealed that the compositional and volumetric alterations in the extracellular matrix are the consequences of aging and may be related to Alzheimer's disease (AD). In this study, we aimed to demonstrate the alterations in hippocampal extracellular fluid proteins in vivo using the 5XFAD mouse model. Samples were obtained from hippocampi of 5XFAD mice (n = 6) and their non-transgenic littermates by intracerebral push-pull perfusion technique at 3 months of age, representing the pre-pathological stage of the AD. Proteins in the hippocampal perfusates were analyzed by Ultra Performance Liquid Chromatography-Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (UPLC-ESI-qTOF-MS/MS). 178 proteins were identified and 19 proteins of them were found to be statistically significantly altered (p <= 0.05, fold change>= 40%, unique peptide count>= 3) in the hippocampal CA1 extracellular fluid of the 5XFAD mouse model. Ingenuity pathway analysis of the protein expression results identified IL6 as an upstream regulator. The upregulation of IL6 was validated by immunohistochemical staining of the hippocampus and cortex of the 5XFAD mice prior to A beta plaque formation. Furthermore, the iron level in the hippocampus was measured by inductively coupled plasma-mass spectrometry as IL6 is mentioned in several studies to take part in iron homeostasis and inflammation and found to be increased in 5XFAD mice hippocampus. Alterations in extracellular matrix proteins in addition to increasing amount of hippocampal IL6 and iron in the early stages of AD may reveal inflammation-mediated iron dyshomeostasis in the early stages of neurodegeneration.
dc.description.sponsorshipTUBITAK (Turkey) - ARRS (Slovenia) Bilateral Cooperation program [112S414]en_US
dc.description.sponsorshipThis study is supported financially by TUBITAK (Turkey) - ARRS (Slovenia) Bilateral Cooperation program with 112S414 project number. Special thanks to Assoc. Prof. Dr. Ozge Cevik for providing us IL6 antibody.en_US
dc.identifier.citationGürel, B., Cansev, M., Sevinç, C., Keleştemur, S., Öçalan, B., Çakır, A. ... Baykal, A. (2018). Early stage alterations in CA1 extracellular region proteins indicate dysregulation of IL6 and iron homeostasis in the 5XFAD Alzheimer's disease mouse model. Journal of Alzheimers Disease, 61(4), 1399-1410. https://dx.doi.org/10.3233/JAD-170329
dc.identifier.doi10.3233/JAD-170329
dc.identifier.endpage1409
dc.identifier.issn1387-2877
dc.identifier.issn1875-8908
dc.identifier.issue4
dc.identifier.scopusqualityQ1
dc.identifier.startpage1399
dc.identifier.urihttps://dx.doi.org/10.3233/JAD-170329
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2947
dc.identifier.volume61
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherIos Press
dc.relation.ecinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/112S414
dc.relation.ispartofJournal of Alzheimers Diseaseen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAlzheimer's Disease
dc.subjectExtracellular Matrix
dc.subjectIL6
dc.subjectIron
dc.subjectNeuroinflammation
dc.subjectProteomics
dc.titleEarly stage alterations in CA1 extracellular region proteins indicate dysregulation of IL6 and iron homeostasis in the 5XFAD Alzheimer's disease mouse model
dc.typeArticle

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