Early stage alterations in CA1 extracellular region proteins indicate dysregulation of IL6 and iron homeostasis in the 5XFAD Alzheimer's disease mouse model
| Autor: | Mehmet Cansev, Sami Aydin, Ismail H. Ulus, Nevzat Kahveci, Ozlem Taskapilioglu, Busra Ocalan, Busra Gurel, Mehmet Ozansoy, Mete Bora Tuzuner, Aysen Cakir, Merve Karayel Basar, Cansu Sevinc, Seda Kelestemur, Ahmet Tarik Baykal, Betul Sahin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteomics Iron Mice Transgenic Hippocampal formation Alzheimer's Disease Extracellular matrix 03 medical and health sciences Mice 0302 clinical medicine Neuroinflammation Alzheimer Disease Tandem Mass Spectrometry Extracellular fluid medicine Extracellular Hippocampus (mythology) Animals Homeostasis CA1 Region Hippocampal Chemistry Interleukin-6 General Neuroscience Neurodegeneration General Medicine medicine.disease Fold change IL6 Cell biology Extracellular Matrix Psychiatry and Mental health Clinical Psychology Disease Models Animal 030104 developmental biology Female Geriatrics and Gerontology 030217 neurology & neurosurgery Chromatography Liquid |
| Popis: | WOS: 000423364400015 PubMed ID: 29376847 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 = 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. TUBITAK (Turkey) - ARRS (Slovenia) Bilateral Cooperation program [112S414] This 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. |
| Databáze: | OpenAIRE |
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