Increased tau phosphorylation follows impeded dopamine clearance in a P301L and novel P301L/COMT-deleted (DM) tau mouse model

Journal of Neurochemistry
Jeremy KoppelPeter Davies

Abstract

In Alzheimer's disease, the phosphorylation of tau is a critical event preceding the formation of neurofibrillary tangles. Previous work exploring the impact of a dopamine blocking antipsychotic on tau phosphorylation in a tau transgenic model suggested that extracellular dopamine may play a regulatory role in the phosphorylation state of tau. In order to test this hypothesis, and in order to develop a mouse model of impaired dopamine metabolism and tauopathy, an extant P301L transgenic tau model of Alzheimer's disease and a novel P301L/catechol-O-methyltransferase deleted model (DM mouse) were treated with the norepinephrine reuptake inhibitor reboxetine, and prefrontal dopamine concentrations and the phosphorylated state of tau was quantified. In two experiments, male and female P301L+/+//COMT+/+ and P301L+/+//COMT-/- (DM) mice were treated with reboxetine 20 mg/kg IP. In one experiment, acutely following reboxetine injection, the prefrontal cortex of mice were microdialyzed for dopamine, and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, utilizing the MetaQuant technique. In another experiment, acutely following reboxetine injections, tau phosphorylation was quantified in the frontal cortex, striatum,...Continue Reading

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Citations

Jan 27, 2021·Neuroscience and Biobehavioral Reviews·Francesco Fornai, Stefano Puglisi-Allegra
May 4, 2021·Journal of Alzheimer's Disease : JAD·Xin WangJian-Zhi Wang
Nov 27, 2021·Neuropathology and Applied Neurobiology·Emily J KollerParamita Chakrabarty

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