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dc.contributor.authorKacířová, Miroslava
dc.contributor.authorŽelezná, Blanka
dc.contributor.authorBlažková, Michaela
dc.contributor.authorHolubová, Martina
dc.contributor.authorPopelová, Andrea
dc.contributor.authorKuneš, Jaroslav
dc.contributor.authorŠedivá, Blanka
dc.contributor.authorMaletínská, Lenka
dc.date.accessioned2021-10-04T10:00:12Z-
dc.date.available2021-10-04T10:00:12Z-
dc.date.issued2021
dc.identifier.citationKACÍŘOVÁ, M. ŽELEZNÁ, B. BLAŽKOVÁ, M. HOLUBOVÁ, M. POPELOVÁ, A. KUNEŠ, J. ŠEDIVÁ, B. MALETÍNSKÁ, L. Aging and high-fat diet feeding lead to peripheral insulin resistance and sexdependent changes in brain of mouse model of tau pathology THY-Tau22. Journal of Neuroinflammation, 2021, roč. 18, č. 1, s. nestránkováno. ISSN: 1742-2094cs
dc.identifier.issn1742-2094
dc.identifier.uri2-s2.0-85109060255
dc.identifier.urihttp://hdl.handle.net/11025/45430
dc.format22 s.cs
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherSpringeren
dc.relation.ispartofseriesJournal of Neuroinflammationen
dc.titleAging and high-fat diet feeding lead to peripheral insulin resistance and sexdependent changes in brain of mouse model of tau pathology THY-Tau22en
dc.typečlánekcs
dc.typearticleen
dc.rights.accessopenAccessen
dc.type.versionpublishedVersionen
dc.description.abstract-translatedBackground Obesity leads to low-grade inflammation in the adipose tissue and liver and neuroinflammation in the brain. Obesity-induced insulin resistance (IR) and neuroinflammation seem to intensify neurodegeneration including Alzheimer's disease. In this study, the impact of high-fat (HF) diet-induced obesity on potential neuroinflammation and peripheral IR was tested separately in males and females of THY-Tau22 mice, a model of tau pathology expressing mutated human tau protein. Methods Three-, 7-, and 11-month-old THY-Tau22 and wild-type males and females were tested for mobility, anxiety-like behavior, and short-term spatial memory in open-field and Y-maze tests. Plasma insulin, free fatty acid, cholesterol, and leptin were evaluated with commercial assays. Liver was stained with hematoxylin and eosin for histology. Brain sections were 3 ',3 '-diaminobenzidine (DAB) and/or fluorescently detected for ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and tau phosphorylated at T231 (pTau (T231)), and analyzed. Insulin signaling cascade, pTau, extracellular signal-regulated kinase 1/2 (ERK1/2), and protein phosphatase 2A (PP2A) were quantified by western blotting of hippocampi of 11-month-old mice. Data are mean +/- SEM and were subjected to Mann-Whitney t test within age and sex and mixed-effects analysis and Bonferroni's post hoc test for age comparison. Results Increased age most potently decreased mobility and increased anxiety in all mice. THY-Tau22 males showed impaired short-term spatial memory. HF diet increased body, fat, and liver weights and peripheral IR. HF diet-fed THY-Tau22 males showed massive Iba1+ microgliosis and GFAP+ astrocytosis in the hippocampus and amygdala. Activated astrocytes colocalized with pTau (T231) in THY-Tau22, although no significant difference in hippocampal tau phosphorylation was observed between 11-month-old HF and standard diet-fed THY-Tau22 mice. Eleven-month-old THY-Tau22 females, but not males, on both diets showed decreased synaptic and postsynaptic plasticity. Conclusions Significant sex differences in neurodegenerative signs were found in THY-Tau22. Impaired short-term spatial memory was observed in 11-month-old THY-tau22 males but not females, which corresponded to increased neuroinflammation colocalized with pTau(T231) in the hippocampi and amygdalae of THY-Tau22 males. A robust decrease in synaptic and postsynaptic plasticity was observed in 11-month-old females but not males. HF diet caused peripheral but not central IR in mice of both sexes.en
dc.subject.translatedAlzheimer's diseaseen
dc.subject.translatedTHY-Tau22 mouseen
dc.subject.translatedObesityen
dc.subject.translatedNeuroinflammationen
dc.subject.translatedPeripheral insulin resistanceen
dc.subject.translatedSex differencesen
dc.identifier.doi10.1186/s12974-021-02190-3
dc.type.statusPeer-revieweden
dc.identifier.document-number664491200001
dc.identifier.obd43933264
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