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Aging and high-fat diet feeding lead to peripheral insulin resistance and sex-dependent changes in brain of mouse model of tau pathology THY-Tau22
M. Kacířová, B. Železná, M. Blažková, M. Holubová, A. Popelová, J. Kuneš, B. Šedivá, L. Maletínská
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
RVO:61388963
Ústav Organické Chemie a Biochemie, Akademie Věd České Republiky
RVO:61388963
Ústav Organické Chemie a Biochemie, Akademie Věd České Republiky
RVO:67985823
Akademie Věd České Republiky
RVO:67985823
Akademie Věd České Republiky
20-00546S
Grantová Agentura České Republiky
20-00546S
Grantová Agentura České Republiky
BioMedCentral Open Access od 2004
Directory of Open Access Journals od 2004
Free Medical Journals od 2004
PubMed Central od 2004
Europe PubMed Central od 2004
ProQuest Central od 2009-01-01
Open Access Digital Library od 2004-01-01
Open Access Digital Library od 2004-04-01
Open Access Digital Library od 2004-01-01
Health & Medicine (ProQuest) od 2009-01-01
Springer Journals Complete - Open Access od 2004-12-01
Springer Nature OA/Free Journals od 2004-12-01
Odkazy
PubMed
34158075
DOI
10.1186/s12974-021-02190-3
Knihovny.cz E-zdroje
- MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- fosforylace MeSH
- hipokampus metabolismus MeSH
- inzulinová rezistence * MeSH
- krátkodobá paměť MeSH
- modely nemocí na zvířatech MeSH
- mozek metabolismus patofyziologie MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- obezita komplikace etiologie MeSH
- omezení pohyblivosti MeSH
- proteiny tau MeSH
- sexuální faktory MeSH
- stárnutí metabolismus MeSH
- tauopatie komplikace genetika MeSH
- zánět MeSH
- ztučnělá játra metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: 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.
Department of Mathematics University of West Bohemia Univerzitní 2732 8 301 00 Pilsen Czech Republic
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