Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease

Emilie Faivre, Joana E. Coelho, Katja Zornbach, Enas Malik, Younis Baqi, Marion Schneider, Lucrezia Cellai, Kevin Carvalho, Shéhérazade Sebda, Martin Figeac, Sabiha Eddarkaoui, Raphaëlle Caillierez, Yijuang Chern, Michael Heneka, Nicolas Sergeant, Christa E. Müller, Annett Halle, Luc Buée, Luisa V. Lopes, David Blum*

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةArticleمراجعة النظراء

65 اقتباسات (Scopus)

ملخص

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.

اللغة الأصليةEnglish
رقم المقال235
دوريةFrontiers in Molecular Neuroscience
مستوى الصوت11
المعرِّفات الرقمية للأشياء
حالة النشرPublished - يوليو 12 2018

ASJC Scopus subject areas

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