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 - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85051290447&partnerID=8YFLogxK
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 -