Seminar – David Blum

Venue: Centre Broca Nouvelle-Aquitaine

David Blum
UMR Inserm UMR-S1172 – Lille
http://blumda.free.fr/

Invited by : Eric Boué-Grabot
Directeur de recherche / IMN

Abstract

Consumption of caffeine, a non-selective antagonist of adenosine A_2A receptor (A_2AR), 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 A_2AR blockade improves memory and pathology in transgenic models mimicking Tau and amyloid lesions. These data not only support A_2A receptor as a valuable target in AD but also suggest that A_2A receptors are involved in the pathophysiological development of the disease. Beneficial effects of caffeine and A_2AR antagonists are presumably ascribed to the normalization of dysregulated A_2AR activity. Indeed, brains of aged and AD individuals but also AD models are characterized by an abnormal upsurge of A_2ARs, being of neuronal and astrocytic origin. However, respective impact of neuronal and astrocytic A_2AR 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 A_2AR function towards cognition and brain lesions in transgenic models of AD.

Recent publications

1. Laurent C*, Burnouf S*, Ferry B, Batalha V, Coehlo J, Baqi Y, Malik E, Marciniak E, Parrot S, Van der Jeugd A, Faivre E, Flaten V, Ledent C, d’Hooge R, Sergeant N, Hamdane M, Humez S, Müller CE, Lopes LV, Buée L & Blum D (2016) A_2A adenosine receptor deletion is protective in a mouse model of Tauopathy. Molecular Psychiatry 21(1):97-107. doi: 10.1038/mp.2015.115.
2. 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.
3. 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.
4. 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.
5. 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