Venue: Centre Broca Nouvelle-Aquitaine
UMR Inserm UMR-S1172 – Lille
Invited by : Eric Boué-Grabot
Directeur de recherche / IMN
Consumption of caffeine, a non-selective antagonist of adenosine A2A receptor (A2AR), mitigates cognitive decline during ageing, reduces Alzheimer’s disease (AD) risk in Humans, and also decreases amyloid and Tau pathologies in AD transgenic mouse models. In line, selective A2AR blockade improves memory and pathology in transgenic models mimicking Tau and amyloid lesions. These data not only support A2A receptor as a valuable target in AD but also suggest that A2A receptors are involved in the pathophysiological development of the disease. Beneficial effects of caffeine and A2AR antagonists are presumably ascribed to the normalization of dysregulated A2AR activity. Indeed, brains of aged and AD individuals but also AD models are characterized by an abnormal upsurge of A2ARs, being of neuronal and astrocytic origin. However, respective impact of neuronal and astrocytic A2AR dysregulations towards development of cognitive deficits and AD lesions remains largely unknown. Our current project is to provide new insights on the impact of neuronal and astroglial gain of A2AR function towards cognition and brain lesions in transgenic models of AD.
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- Laurent C, Dorothée G, Hunot S, Martin E, Monnet Y, Duchamp M, Dong Y, Legeron FP, Leboucher A, Burnouf S, Faivre E, Carvalho K, Caillierez R, Zommer N, Demeyer D, Jouy N, Sazdovitch V, Schraen-Maschke S, Delarasse C, Buée L & Blum D (2017) Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of Tauopathy. Brain 140(Pt 1):184-200. doi: 10.1093/brain/aww270.
- Marciniak E, Leboucher A, Caron E, Ahmed T, Tailleux A, Dumont J, Issad T, Gerhardt E, Pagesy P, Vileno M, Bournonville C, Hamdane M, Bantubungi K, Lancel S, Demeyer D, Eddarkaoui S, Vallez A, Vieau D, Humez S, Faivre E, Grenier-Boley B, Outeiro TH, Staels B, Amouyel P, Balschun D, Buee L & Blum D (2017). Tau deletion promotes brain insulin resistance (2017) The Journal of Experimental Medicine 214(8):2257-2269. doi: 10.1084/jem.20161731.
- Temido-Ferreira M, Ferreira DG, Batalha VL, Marques-Morgado I, Coelho JE, Pereira P, Gomes R, Carvalho S, Canas PM, Cuvelier L, Buée-Scherrer V, Faivre E, Baqi Y, Müller CE, Pimentel J, Schiffmann SN, Buée L, Bader M, Outeiro TF, Blum D, Cunha RA, Marie H, Pousinha PA and Lopes LV (2018) The age-related shift in LTD induction is mediated by adenosine A2A receptors through NMDA receptors and Ca2+ dysregulation. Molecular Psychiatry (in press). doi: 10.1038/s41380-018-0110-9.
- Chatterjee S, Schneider-Anthony A, Cassel R, Merienne K, Cosquer B, Sinha S, Kumar M, Chaturderby P, Eswaramoorthy M, Le Gras S, Keime C, Dutar P, Petsophonsakul P, Rampon C, Cassel JC, Buée L, Blum D, Kundu TK & Boutillier AL (2018) Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator. EMBO Mol Med (in press).pii: e8587. doi: 10.15252/emmm.201708587