Synaptic and memory dysfunction in a β-amyloid model of early Alzheimer's disease depends on increased formation of ATP-derived extracellular adenosine.

Neurobiology of Disease
Francisco Q GonçalvesRodrigo A Cunha

Abstract

Adenosine A2A receptors (A2AR) overfunction causes synaptic and memory dysfunction in early Alzheimer's disease (AD). In a β-amyloid (Aβ1-42)-based model of early AD, we now unraveled that this involves an increased synaptic release of ATP coupled to an increased density and activity of ecto-5'-nucleotidase (CD73)-mediated formation of adenosine selectively activating A2AR. Thus, CD73 inhibition with α,β-methylene-ADP impaired long-term potentiation (LTP) in mouse hippocampal slices, which is occluded upon previous superfusion with the A2AR antagonist SCH58261. Furthermore, α,β-methylene-ADP did not alter LTP amplitude in global A2AR knockout (KO) and in forebrain neuron-selective A2AR-KO mice, but inhibited LTP amplitude in astrocyte-selective A2AR-KO mice; this shows that CD73-derived adenosine solely acts on neuronal A2AR. In agreement with the concept that ATP is a danger signal in the brain, ATP release from nerve terminals is increased after intracerebroventricular Aβ1-42 administration, together with CD73 and A2AR upregulation in hippocampal synapses. Importantly, this increased CD73 activity is critically required for Aβ1-42 to impair synaptic plasticity and memory since Aβ1-42-induced synaptic and memory deficits were ...Continue Reading

Citations

May 20, 2020·British Journal of Pharmacology·Kenneth A JacobsonJens Carlsson
Aug 4, 2020·The Journal of Pharmacy and Pharmacology·Ping LiuXinyu Bai
Jun 23, 2020·Journal of Caffeine and Adenosine Research·Fabio C TescarolloDetlev Boison
Sep 26, 2020·Frontiers in Cellular Neuroscience·Rebecca StevensonYossi Buskila
Jun 26, 2020·Frontiers in Molecular Neuroscience·Linda FrancistiováMiguel Díaz-Hernández
Feb 3, 2021·The Journal of Gene Medicine·Miaomiao ZhouPingyi Xu
Mar 2, 2021·Journal of Alzheimer's Disease : JAD·Stefania MerighiStefania Gessi
Apr 9, 2021·Frontiers in Pharmacology·Stefania MerighiStefania Gessi
Dec 18, 2020·Biochemical Pharmacology·Cátia R LopesPaula M Canas
Jun 3, 2021·Cells·Stefania MerighiDavide Ferrari
Jun 1, 2021·Frontiers in Neuroscience·Cátia R LopesPaula Agostinho
Jun 1, 2021·Frontiers in Pharmacology·Mercedes Garcia-GilMaria Grazia Tozzi
Jun 1, 2021·Frontiers in Neurology·Marie J PietrowskiKevin Carvalho
Jul 4, 2021·Purinergic Signalling·Aderbal S AguiarRodrigo A Cunha
Jul 24, 2021·European Journal of Pharmacology·Anusha GovindulaJayesh Mudgal
Aug 3, 2021·Frontiers in Neuroscience·Ana Moreira-de-SáRodrigo A Cunha
Jul 21, 2021·ACS Chemical Neuroscience·Siwei ChenAmal Alachkar
Jul 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marlene F PereiraPaula Agostinho

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