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• W1959171036 startingPage "448" @default.
• W1959171036 abstract "Clinical studies suggest that exposure to stress can increase risk for Alzheimer’s disease (AD). Although the precise links between stress and vulnerability to develop AD remain uncertain, recent animal work suggests that stress may promote susceptibility to AD pathology by activating tau kinases and inducing tau phosphorylation (tau-P). Our previous findings indicate the differential involvement of corticotropin-releasing factor receptor (CRFR) types 1 and 2 in regulating tau-P in the hippocampus induced by acute restraint, an emotional stressor. To assess the generality of CRFR involvement in stress-induced tau-P and tau kinase activity, the present study extends our investigation to a well-characterized physiological stressor, i.e. immune challenge induced by bacterial lipopolysaccharide (LPS). Acute systemic administration of LPS (100 μg/kg) robustly increased hippocampal (but not isocortical or cerebellar) tau-P, peaking at 40–120 min postinjection and abating thereafter. Assessments of the genotype dependence of this effect yielded results that were distinct from the restraint model. Treatment with LPS increased phosphorylation in wild-type, single and double CRFR knockouts with only subtle variation, which included a reliable exaggeration of tau-P responses in CRFR1-deficient mice. Parallel analyses implicated glycogen synthase kinase-3 and cyclin-dependent kinase-5 as likely cellular mediators of LPS-induced tau-P. Conversely, our data suggest that temperature-dependent fluctuations in tau protein phosphatase 2A (PP2A) may not play a role in this context. Thus, neither the strict CRFR1 dependence of restraint-induced tau-P nor the exaggeration of these responses in CRFR2 null mice generalize to the LPS model. CRFR mediation of stress-induced hippocampal tau-P may be limited to emotional stressors." @default.
• W1959171036 created "2016-06-24" @default.
• W1959171036 creator A5019285186 @default.
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• W1959171036 date "2011-07-04" @default.
• W1959171036 modified "2023-10-06" @default.
• W1959171036 title "Lipopolysaccharide-induced tau phosphorylation and kinase activity - modulation, but not mediation, by corticotropin-releasing factor receptors" @default.
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• W1959171036 doi "https://doi.org/10.1111/j.1460-9568.2011.07764.x" @default.
• W1959171036 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3148267" @default.
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• W1959171036 hasPublicationYear "2011" @default.
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