Allergy influences the inflammatory status of the brain and enhances tau-phosphorylation
Heela Sarlus
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCaroline Olgart Höglund
Respiratory Medicine Unit, Lung Research Laboratory, L4:01, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
Section for Neuroimmunology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Osher Center for Integrative Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorBianka Karshikoff
Respiratory Medicine Unit, Lung Research Laboratory, L4:01, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
Section for Neuroimmunology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Osher Center for Integrative Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorXiuzhe Wang
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMats Lekander
Stress Research Institute, Stockholm University, Stockholm, Sweden
Osher Center for Integrative Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMarianne Schultzberg
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Mircea Oprica
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
Correspondence to: Mircea OPRICA, Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, floor 5, SE-141 86 Stockholm, Sweden.
Tel.: +46-8-585 83881
Fax: +46-8-585 83880
E-mail: [email protected]
Search for more papers by this authorHeela Sarlus
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCaroline Olgart Höglund
Respiratory Medicine Unit, Lung Research Laboratory, L4:01, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
Section for Neuroimmunology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Osher Center for Integrative Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorBianka Karshikoff
Respiratory Medicine Unit, Lung Research Laboratory, L4:01, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
Section for Neuroimmunology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Osher Center for Integrative Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorXiuzhe Wang
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMats Lekander
Stress Research Institute, Stockholm University, Stockholm, Sweden
Osher Center for Integrative Medicine and Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMarianne Schultzberg
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Mircea Oprica
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
Correspondence to: Mircea OPRICA, Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, floor 5, SE-141 86 Stockholm, Sweden.
Tel.: +46-8-585 83881
Fax: +46-8-585 83880
E-mail: [email protected]
Search for more papers by this authorAbstract
Despite the existing knowledge regarding the neuropathology of Alzheimer's disease (AD), the cause of sporadic forms of the disease is unknown. It has been suggested that systemic inflammation may have a role, but the exact mechanisms through which inflammatory processes influence the pathogenesis and progress of AD are not obvious. Allergy is a chronic inflammatory disease affecting more than 20% of the Western population, but the effects of allergic conditions on brain functions are largely unknown. The aim of this study was to investigate whether or not chronic peripheral inflammation associated with allergy affects the expression of AD-related proteins and inflammatory markers in the brain. On the basis of previously described models for allergy in mice we developed a model of chronic airway allergy in mouse, with ovalbumin as allergen. The validity of the chronic allergy model was confirmed by a consistent and reproducible eosinophilia in the bronchoalveolar lavage (BAL) fluid of allergic animals. Allergic mice were shown to have increased brain levels of both immunoglobulin (Ig) G and IgE with a widespread distribution. Allergy was also found to increase phosphorylation of tau protein in the brain. The present data support the notion that allergy-dependent chronic peripheral inflammation modifies the brain inflammatory status, and influences phosphorylation of an AD-related protein, indicating that allergy may be yet another factor to be considered for the development and/or progression of neurodegenerative diseases such as AD.
Supporting Information
| Filename | Description |
|---|---|
| jcmm1556-sup-0001-FigS1a.tifimage/tif, 612.1 KB | Figure S1 The effects of chronic airway-induced allergy on the estimation of the total number of cells and of eosinophils in the bronchoalveolar lavage (BAL) fluid from Balb/c (A) and C57B6 (B) mice. |
| jcmm1556-sup-0002-FigS1b.tifimage/tif, 577.2 KB | |
| jcmm1556-sup-0003-FigS2a-e.tifimage/tif, 4.3 MB | Figure S2 The effects of chronic airway-induced allergy on the brain levels of IgG (A – E) and IgE (A) as shown by immunoblotting (A) and immunohistochemistry (B–E) in C57B6 mice. |
| jcmm1556-sup-0004-FigS3a.tifimage/tif, 644.4 KB | Figure S3 The effects of chronic airway-induced allergy on the levels of TH1/TH2 cytokines (interleukin (IL)-1b, -2, -4, -5, -8, -10, -12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α), in the hippocampus (A) and parietal cortex (B) of C57B6 mice, as measured by Mesoscale assay. |
| jcmm1556-sup-0005-FigS3b.tifimage/tif, 616.4 KB | |
| jcmm1556-sup-0006-FigS4.tifimage/tif, 2.1 MB | Figure S4 The effects of chronic airway-induced allergy on the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of C57B6 mice as determined by immunoblotting. |
| jcmm1556-sup-0007-FigS5a-d.tifimage/tif, 4.2 MB | Figure S5 The effects of chronic airway-induced allergy on tau-phosphorylation at the AT8 (A and B) and AT180 (C and D) phosphorylation sites in the hippocampus (A and C) and parietal cortex (B and D) of C57B6 mice. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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