@article{4c58455ac50c44a09031fded852f30aa,
title = "A2A adenosine receptor deletion is protective in a mouse model of Tauopathy",
abstract = "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.",
author = "C. Laurent and S. Burnouf and B. Ferry and Batalha, {V. L.} and Coelho, {J. E.} and Y. Baqi and E. Malik and E. Mariciniak and S. Parrot and {Van Der Jeugd}, A. and E. Faivre and V. Flaten and C. Ledent and R. D'Hooge and N. Sergeant and M. Hamdane and S. Humez and M{\"u}ller, {C. E.} and Lopes, {L. V.} and L. Bu{\'e}e and D. Blum",
note = "Funding Information: This work was supported by grants from France Alzheimer (to DB) and LECMA/ Alzheimer Forschung Initiative (to DB and CEM). DB and LVL got a {\'E}gide/Pessoa program EU exchange grant. Our laboratory is also supported by the LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer{\textquoteright}s disease), Inserm, CNRS, Universit{\'e} Lille 2, Lille M{\'e}tropole Communaut{\'e} Urbaine, R{\'e}gion Nord/Pas-de-Calais, FEDER, DN2M, ANR (ADONTAGE and ADORATAU, to DB) and FUI MEDIALZ. We thank the animal facility of IMPRT-IFR114 and M Besegher, I Brion, D Cappe, R Dehaynin, J Devassine, Y Lepage, C Meunier and D Taillieu for transgenic mouse production and animal care, as well as M Basquin, D Demeyer, S Eddarkaoui, H Obriot and M Schneider for support. CL holds a doctoral grant from Lille 2 University, and SB from R{\'e}gion Nord Pas de Calais and CHRU de Lille. VF holds a grant from R{\'e}gion Nord-Pas-de-Calais and Inserm. EF holds a post-doctoral grant from R{\'e}gion Nord-Pas-de-Calais (DN2M). LVL is an Investigator FCT (Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia, Portugal). Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited All rights reserved.",
year = "2016",
month = jan,
day = "1",
doi = "10.1038/mp.2014.151",
language = "English",
volume = "21",
pages = "97--107",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "1",
}