Early stage alterations in CA1 extracellular region proteins indicate dysregulation of IL6 and iron homeostasis in the 5XFAD Alzheimer's disease mouse model
Date
2018
Authors
Gürel, Büşra
Keleştemur, Seda
Ozansoy, Mehmet
Ulus, İsmail Hakkı
Başar, Merve Karayel
Şahin, Betül
Tuzuner, Mete Bora
Baykal, Ahmet Tarık
Journal Title
Journal ISSN
Volume Title
Publisher
IOS Press
Abstract
In 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.
Description
Keywords
Neurosciences & neurology, Alzheimer's disease, Extracellular matrix, IL6, Iron, Neuroinflammation, Proteomics, Mild cognitive impairment, Cerebrospinal-fluid, Parkinsons-disease, Proteomic analysis, Perineuronal nets, Oxidative stress, Transgenic mice, Brain, Inflammation, Receptor
Citation
Gürel, B. vd. (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 Alzheimer's Disease, 61(4), 1399-1410.