Association Between Adenosine A2A Receptors and Connexin 43 Regulates Hemichannels Activity and ATP Release in Astrocytes Exposed to Amyloid-β Peptides

CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A2A Receptor-Mediated Control of Fear Memory and Amygdala Plasticity

“…Indeed, previous studies have described a similar tight association between CD73 activity and the activation of A 2A R during neurodevelopment [ 49 ], in circuits of the dorsal striatum [ 32 , 50 ] and of the normal [ 25 ] or diseased hippocampus [ 26 , 51 ], supported by the physical association of A 2A R and CD73 in the striatum [ 24 ]. A similar association of CD73 and A 2A R was concluded in other cells or tissues such as neuromuscular junction [ 52 ], astrocytes [ 53 ], “activated” microglia [ 54 , 55 ], neutrophils [ 56 ], B cell lymphocytes [ 57 ], T cell lymphocytes [ 58 ], fibroblasts [ 59 ], cardiac valve interstitial cells [ 60 ] or mesenchymal stem cells [ 61 ]. Overall, this evidence supports a general association of CD73-mediated formation of extracellular adenosine with the activation of A 2A R, although an association of CD73 activity with A 2B R has been described in some tissues/cells where A 2B R-mediated responses are predominant, such as osteoblasts [ 62 ], dendritic cells [ 63 ] or glioblastoma cells [ 64 ].…”

Impact of blunting astrocyte activity on hippocampal synaptic plasticity in a mouse model of early Alzheimer's disease based on amyloid‐β peptide exposure

“…Several of these astrocytic processes are affected upon exposure of astrocytes to Aβ, namely, an increase of the release of glutamate and ATP from astrocytes (Madeira et al, 2021;Pham et al, 2021), a modification of astrocytic metabolism (Allaman et al, 2010), or a decreased density of glutamate transporters in astrocytes (Huang et al, 2018;Matos et al, 2012). However, most of these mechanisms have been proposed to control hippocampal LTP, and comparatively little is known about the mechanisms underlying the control by astrocytes of hippocampal LTD (Navarette et al, ;Omrani et al, 2009;Zhang et al, 2008;reviewed in Durkee et al, 2021).…”

Increased Synaptic ATP Release and CD73-Mediated Formation of Extracellular Adenosine in the Control of Behavioral and Electrophysiological Modifications Caused by Chronic Stress

“…This implies an overfunction of purinergic A 2A R and P 2X7 R, which apparently contrasts with the proposed antidepressant role of ATP based on the reported decreased ATP levels associated with depression. − This is particularly surprising since ATP is a danger signal in the brain (reviewed in ref ), and there is an increased ATP release in different brain diseases, ,,, in particular in synapses that are particularly affected at the onset of depressive conditions (reviewed in ref ). Notably, the observed decrease of ATP release in depressive-like conditions was proposed to originate from astrocytes, ,,, which release ATP through lysosome exocytosis, through transmembrane Calhm2 channel proteins, through pannexin-1 channel, and through connexin-43, whereas the release of ATP from nerve terminals is mostly vesicular in nature. − Furthermore, ATP release from astrocytes is designed to entrain a volume-like heterosynaptic depression , and is expected to overshadow the vesicular release of ATP from nerve terminals, which only represent ∼1% of gray matter volume, designed to act within the synapse to bolster synaptic plasticity through A 2A R activation after its local extracellular catabolism by ecto-nucleotidases. − …”