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

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

Evaluation of morphometry-based dating of monogenetic volcanoes: a case study from Bandas del Sur, Tenerife (Canary Islands)

Morphometry-based dating provides a first-order estimate of the temporal evolution of monogenetic volcanic edifices located within an intraplate monogenetic volcanic field or on the flanks of a polygenetic volcano. Two widely used morphometric parameters, namely cone height/width ratio (Hmax/Wco) and slope angle, were applied to extract chronological information and evaluate their accuracy for morphometry-based ordering. Based on these quantitative parameters extracted from contour-based Digital Elevation Models (DEMs), two event orders for the Bandas del Sur in Tenerife (Canary Islands) were constructed and compared with the existing K-Ar, paleomagnetic and stratigraphic data. The results obtained suggest that the commonly used Hmax/Wcoratio is not reliable, leading to inappropriate temporal order estimates, while the slope angle gives slightly better results. The overall performance of such descriptive parameterswas, however, generally poor(i.e. there is no strong correlation between morphometry and age). The geomorphic/morphometric mismatches could be the result of (1) the diversity of syn-eruptive processes (i.e. diverse initial morphologies causing geomorphic/morphometric variability), (2) contrasting, edifice-specific degradation that depends partly upon the inner facies architecture of the volcanic edifices, (3) various external environmental controls (e.g. tephra mantling from pyroclastic density currents unrelated to the edifice evaluated) and (4) differences in the scale/resolution of input data. The observed degradation trend and changes in morphometric parameters over time do not support a simple degradation model for monogenetic scoria cones volcanoes.This research was also partly supported by Department of Geology and Mineral Deposits, University of Miskolc Hungary). AG is grateful for her Juan de la Cierva Grant (JCI-2010-06092). JM is grateful to the MICINN grant CGL2008-04264.Peer Reviewe