ArticleBiological psychiatry2015
Deletion of adenosine A2A receptors from astrocytes disrupts glutamate homeostasis leading to psychomotor and cognitive impairment: relevance to schizophrenia.
Article in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 154 citations in OpenAlex.
- Adenosine A2A receptor signaling in neuroinflammation, glial modulation, and mechanisms associated with chronic pain.Purinergic signalling · 2026Review
- Adenosine AJournal of neurochemistry · 2026Article
- Adenosine A2A signaling in mood disorders: How far have we come?IBRO neuroscience reports · 2025Article
- Upregulation of adenosine AMolecular psychiatry · 2025Article
- Review
- Advances and challenges in experimental models of posttraumatic epilepsy for therapeutic interventions.Pharmacological reviews · 2025Review
- The Role of Astrocytes in Synaptic Dysfunction and Memory Deficits in Alzheimer's Disease.Biomolecules · 2025Review
- Glutamate, a Key for Astrocytes to Participate in Brain Function and Diseases.Neurochemical research · 2025Review
- Review
- Integrated Transcriptome Analysis Reveals Novel Molecular Signatures for Schizophrenia Characterization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.Cell discovery · 2024Article
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- Mitochondrial Dysfunction of Astrocytes Mediates Lipid Accumulation in Temporal Lobe Epilepsy.Aging and disease · 2024Review
- PFOS Elicits Cytotoxicity in Neuron Through Astrocyte-Derived CaMKII-DLG1 Signaling In Vitro Rat Hippocampal Model.Neurochemical research · 2024Article
- Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine ANature communications · 2024Article
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Essential Role of Astrocytes in Learning and Memory.International journal of molecular sciences · 2024Review
- Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).International journal of molecular medicine · 2024Review
- Modification of astrocytic Cx43 hemichannel activity in animal models of AD: modulation by adenosine ACellular and molecular life sciences : CMLS · 2023Article
- Modulation of Neuron and Astrocyte Dopamine Receptors via Receptor-Receptor Interactions.Pharmaceuticals (Basel, Switzerland) · 2023Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAdenosine A2A receptors (A2AR) modulate dopamine and glutamate signaling and thereby may influence some of the psychomotor and cognitive processes associated with schizophrenia. Because astroglial A2AR regulate the availability of glutamate, we hypothesized that they might play an unprecedented role in some of the processes leading to the development of schizophrenia, which we investigated using a mouse line with a selective deletion of A2AR in astrocytes (Gfa2-A2AR knockout [KO] mice].
methodsWe examined Gfa2-A2AR KO mice for behaviors thought to recapitulate some features of schizophrenia, namely enhanced MK-801 psychomotor response (positive symptoms) and decreased working memory (cognitive symptoms). In addition, we probed for neurochemical alterations in the glutamatergic circuitry, evaluating glutamate uptake and release and the levels of key proteins defining glutamatergic signaling (glutamate transporter-I [GLT-I], N-methyl-D-aspartate receptors [NMDA-R] and α-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPA-R]) to provide a mechanistic understanding of the phenotype encountered.
resultsWe show that Gfa2-A2AR KO mice exhibited enhanced MK-801 psychomotor response and decreased working memory; this was accompanied by a disruption of glutamate homeostasis characterized by aberrant GLT-I activity, increased presynaptic glutamate release, NMDA-R 2B subunit upregulation, and increased internalization of AMPA-R. Accordingly, selective GLT-I inhibition or blockade of GluR1/2 endocytosis prevented the psychomotor and cognitive phenotypes in Gfa2-A2AR KO mice, namely in the nucleus accumbens.
conclusionsThese results show that the dysfunction of astrocytic A2AR, by controlling GLT-I activity, triggers an astrocyte-to-neuron wave of communication resulting in disrupted glutamate homeostasis, thought to underlie several endophenotypes relevant to schizophrenia.
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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.