A2A adenosine receptor deletion is protective in a mouse model of Tauopathy.

摘要: Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk developing Alzheimer's disease (AD) in humans and mitigates both amyloid Tau burden transgenic mouse models. However, impact selective A2AR blockade on progressive development AD-related lesions associated memory impairments has not been investigated. In present study, we removed gene encoding from THY-Tau22 mice analysed subsequent effects pathological (Tau phosphorylation aggregation, neuro-inflammation) functional (spatial learning memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect pathology-induced deficits terms spatial long-term depression. These were concomitant with normalization glutamate/gamma-amino butyric acid ratio, together global reduction neuro-inflammatory markers decrease hyperphosphorylation. Additionally, oral therapy using specific antagonist (MSX-3) significantly improved reduced hyperphosphorylation mice. By showing genetic or pharmacological improves phenotype model, data highlight receptors as important molecular targets to consider against AD Tauopathies.