TY - JOUR
T1 - Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease
AU - Faivre, Emilie
AU - Coelho, Joana E.
AU - Zornbach, Katja
AU - Malik, Enas
AU - Baqi, Younis
AU - Schneider, Marion
AU - Cellai, Lucrezia
AU - Carvalho, Kevin
AU - Sebda, Shéhérazade
AU - Figeac, Martin
AU - Eddarkaoui, Sabiha
AU - Caillierez, Raphaëlle
AU - Chern, Yijuang
AU - Heneka, Michael
AU - Sergeant, Nicolas
AU - Müller, Christa E.
AU - Halle, Annett
AU - Buée, Luc
AU - Lopes, Luisa V.
AU - Blum, David
N1 - Funding Information:
This work was supported by a cross-border grant from LECMA/Alzheimer Forschung Initiative/Vaincre Alzheimer (to DB and CM). We hereby thank Frédéric Leprêtre for submitting transcriptomics data to GEO. EF and KC are supported by Université de Lille, LC was supported by Italian Society of Pharmacology and LabEx DISTALZ.
Publisher Copyright:
© 2018 Faivre, Coelho, Zornbach, Malik, Baqi, Schneider, Cellai, Carvalho, Sebda, Figeac, Eddarkaoui, Caillierez, Chern, Heneka, Sergeant, Müller, Halle, Buée, Lopes and Blum.
PY - 2018/7/12
Y1 - 2018/7/12
N2 - Consumption of caffeine, a non-selective adenosine A2Areceptor (A2AR) antagonist, reduces the risk of developing Alzheimer’s disease (AD) and mitigates both amyloid and Tau lesions in transgenic mouse models of the disease. While short-term treatment with A2AR antagonists have been shown to alleviate cognitive deficits in mouse models of amyloidogenesis, impact of a chronic and long-term treatment on the development of amyloid burden, associated neuroinflammation and memory deficits has never been assessed. In the present study, we have evaluated the effect of a 6-month treatment of APPsw/PS1dE9 mice with the potent and selective A2AR antagonist MSX-3 from 3 to 9-10 months of age. At completion of the treatment, we found that the MSX-3 treatment prevented the development of memory deficits in APP/PS1dE9 mice, without significantly altering hippocampal and cortical gene expressions. Interestingly, MSX-3 treatment led to a significant decrease of Aβ1-42 levels in the cortex of APP/PS1dE9 animals, while Aβ1-40 increased, thereby strongly affecting the Aβ1-42/Aβ1-40 ratio. Together, these data support the idea that A2AR blockade is of therapeutic value for AD.
AB - Consumption of caffeine, a non-selective adenosine A2Areceptor (A2AR) antagonist, reduces the risk of developing Alzheimer’s disease (AD) and mitigates both amyloid and Tau lesions in transgenic mouse models of the disease. While short-term treatment with A2AR antagonists have been shown to alleviate cognitive deficits in mouse models of amyloidogenesis, impact of a chronic and long-term treatment on the development of amyloid burden, associated neuroinflammation and memory deficits has never been assessed. In the present study, we have evaluated the effect of a 6-month treatment of APPsw/PS1dE9 mice with the potent and selective A2AR antagonist MSX-3 from 3 to 9-10 months of age. At completion of the treatment, we found that the MSX-3 treatment prevented the development of memory deficits in APP/PS1dE9 mice, without significantly altering hippocampal and cortical gene expressions. Interestingly, MSX-3 treatment led to a significant decrease of Aβ1-42 levels in the cortex of APP/PS1dE9 animals, while Aβ1-40 increased, thereby strongly affecting the Aβ1-42/Aβ1-40 ratio. Together, these data support the idea that A2AR blockade is of therapeutic value for AD.
KW - A2A
KW - Adenosine receptor
KW - Alzheimer’s disease
KW - Amyloid
KW - Memory
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U2 - 10.3389/fnmol.2018.00235
DO - 10.3389/fnmol.2018.00235
M3 - Article
C2 - 30050407
AN - SCOPUS:85051290447
SN - 1662-5099
VL - 11
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 235
ER -