RESEARCH ARTICLE: Up‐regulation of Adenosine Receptors in the Frontal Cortex in Alzheimer's Disease

Abstract

Adenosine receptors are G-protein coupled receptors which modulate neurotransmitter release, mainly glutamate. Adenosine A(1) and A(2A) receptors were studied in post-mortem human cortex in Alzheimer's disease (AD) and age-matched controls. Total adenosine A(1) receptor number, determined by radioligand binding assay, using [(3)H]DPCPX, was significantly increased in AD cases in early and advanced stages without differences with the progression of the disease. A significant increase of A(1)R (37 kDa) levels was also observed by Western blot in early and advanced stages of AD. In addition, increased numbers of adenosine A(2A) receptors were observed in AD samples as determined by a binding assay using [(3)H]ZM 241385 as a radioligand and by Western blot. Increased binding and protein expression levels of adenosine receptors were not associated with increased mRNA levels coding A(1) and A(2A) receptors. Finally, increased A(1) and A(2A) receptor-mediated response was observed. These results show up-regulation of adenosine A(1) and A(2A) receptors in frontal cortex in AD, associated with sensitization of the corresponding transduction pathways.

Adenosine A2AReceptor Blockade Prevents Synaptotoxicity and Memory Dysfunction Caused by β-Amyloid Peptides via p38 Mitogen-Activated Protein Kinase Pathway

“…These results are relevant for the following three different reasons: (1) they provide evidence that control of a presynaptic modulation system that prevents synaptotoxicity also prevents memory dysfunction, strengthening the hypothesis that synaptic dysfunction is a precocious core modification of AD; (2) they provide additional evidence that A 2A Rs, the density of which is increased in AD (Albasanz et al, 2008), are a novel promising target to control AD; (3) they provide a clear demonstration that neuroprotection afforded by A 2A R blockade is independent of cAMP/PKA transducing system and results suggest that it is instead mediated by p38 MAPK.…”

Modulation of Adenosine Receptors by [60]Fullerene Hydrosoluble Derivative in SK-N-MC Cells

“…However, the corresponding mRNA for A 1 was undetectable in our conditions. A very recent study demonstrates that real-time polymerase chain reaction of the plant gene heat shock transcription factor was fully inhibited in the presence of a fullerene derivative C 60 (OH) 20 possibly by the clear tendency for hydrogen bonding between the nanoparticle and both the dNTPs and ssDNA components of the polymerase chain reaction. 34 As experimental conditions were the same for both A 2 and A 1 receptor mRNA analysis, a direct effect of nanoparticle presence during PCR reaction can be ruled out.…”

Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy

“…It is known that A 2A R expression is sensitive to hypoxia (Kobayashi and Millhorn, 1999), inflammation and other brain insults that can trigger up-regulation of the A 2A R in different brain regions (Chen et al, 2013;Chen et al, 2014). Indeed, the A 2A R up-regulation has been documented in human brains of early PD (Villar-Menendez et al, 2014) and AD (Albasanz et al, 2008;Orr et al, 2015), and animal models of PD (Yu et al, 2008), AD (Orr et al, 2015), HD (Li et al, 2015b), amyotrophic lateral sclerosis (Ng et al, 2015), attention deficit hyperactivity disorder (Pandolfo et al, 2013), chronic unpredictable stress (Kaster et al, 2015). Notably, the upregulation of the A 2A R in disease models were demonstrated in neuronal (particularly the nerve terminals) (Kaster et al, 2015;Li et al, 2015b) and some glial elements (Orr et al, 2015;Yu et al, 2008).…”