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SHR Neuro Krebs Kardio Lipid

Löffler, T; Flunkert, S; Havas, D; Schweinzer, C; Uger, M; Windisch, M; Steyrer, E; Hutter-Paier, B.
Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivo model of Alzheimer's disease.
J Neuroinflammation. 2014; 11(7):84-84 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Löffler Tina
Steyrer Ernst
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Number of Figures: 6
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Abstract:
Beyond cognitive decline, Alzheimer's disease (AD) is characterized by numerous neuropathological changes in the brain. Although animal models generally do not fully reflect the broad spectrum of disease-specific alterations, the APPSL mouse model is well known to display early plaque formation and to exhibit spatial learning and memory deficits. However, important neuropathological features, such as neuroinflammation and lipid peroxidation, and their progression over age, have not yet been described in this AD mouse model. Hippocampal and neocortical tissues of APPSL mice at different ages were evaluated. One hemisphere from each mouse was examined for micro- and astrogliosis as well as concomitant plaque load. The other hemisphere was evaluated for lipid peroxidation (quantified by a thiobarbituric acid reactive substances (TBARS) assay), changes in Aβ abundance (Aβ38, Aβ40 and Aβ42 analyses), as well as determination of aggregated Aβ content (Amorfix A4 assay). Finally, correlation analyses were performed to illustrate the time-dependent correlation between neuroinflammation and Aβ load (soluble, insoluble, fibrils), or lipid peroxidation, respectively. As is consistent with previous findings, neuroinflammation starts early and shows strong progression over age in the APPSL mouse model. An analyses of concomitant Aβ load and plaque deposition revealed a similar progression, and high correlations between neuroinflammation markers and soluble or insoluble Aβ or fibrillar amyloid plaque loads were observed. Lipid peroxidation, as measured by TBARS levels, correlates well with neuroinflammation in the neocortex but not the hippocampus. The hippocampal lipid peroxidation correlated strongly with the increase of LOC positive fiber load, whereas neocortical TBARS levels were unrelated to amyloidosis. These data illustrate for the first time the progression of major AD related neuropathological features other than plaque load in the APPSL mouse model. Specifically, we demonstrate that microgliosis and astrocytosis are prominent aspects of this AD mouse model. The strong correlation of neuroinflammation with amyloid burden and lipid peroxidation underlines the importance of these pathological factors for the development of AD. The new finding of a different relation of lipid peroxidation in the hippocampus and neocortical regions show that the model might contribute to the understanding of complex pathological mechanisms and their interplay in AD.
Find related publications in this database (using NLM MeSH Indexing)
Alzheimer Disease - complications
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - genetics
Animals -
Cytokines - genetics
Cytokines - metabolism
Disease Models, Animal -
Encephalitis - etiology
Encephalitis - pathology
Gene Expression Regulation - genetics
Glial Fibrillary Acidic Protein - metabolism
Hippocampus - pathology
Humans -
Mice -
Mice, Transgenic -
Mutation - genetics
Neocortex - pathology
Thiobarbituric Acid Reactive Substances - metabolism

Find related publications in this database (Keywords)
A beta peptides
A beta oligomers
Microgliosis
Astrocytosis
Lipid peroxidation
Correlation analysis
Transgenic mice
APP(SL)
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