ArticleScientific reports2016
The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
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- Role of Adenosine Receptors in Sleep Deprivation-Induced Depression-Like Behaviors.Biomolecules & therapeutics · 2026Article
- Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.The Journal of physiology · 2026Article
- Genetic associations and candidate functional genes linking depression and obesity: a multi-omics integrative study.Frontiers in genetics · 2026Article
- Adenosine A2A signaling in mood disorders: How far have we come?IBRO neuroscience reports · 2025Article
- Adenosine in the Brain: Recent Progress on Detection, Function, and Translation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Caffeine in Aging Brains: Cognitive Enhancement, Neurodegeneration, and Emerging Concerns About Addiction.International journal of environmental research and public health · 2025Review
- Article
- Targeting the adenosine AChinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- Lateral septum adenosine ANature communications · 2023Article
- Chemobrain: An accelerated aging process linking adenosine AInternational review of neurobiology · 2023Review
- Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis.International journal of molecular sciences · 2022Article
- The Role of the Adenosine System on Emotional and Cognitive Disturbances Induced by Ethanol Binge Drinking in the Immature Brain and the Beneficial Effects of Caffeine.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Adenosine APurinergic signalling · 2022Article
- Intrinsically disordered proteins and proteins with intrinsically disordered regions in neurodegenerative diseases.Biophysical reviews · 2022Review
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Maternal stress programs accelerated aging of the basal ganglia motor system in offspring.Neurobiology of stress · 2020Article
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.