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Deletion of Adenosine A2A Receptors From Astrocytes Disrupts Glutamate Homeostasis Leading to Psychomotor and Cognitive Impairment: Relevance to Schizophrenia
Open accessAbstract
Background Adenosine 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].Methods We 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.Results We 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.Conclusions These 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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“In line with this, transgenic mice lacking the A2A receptor or AD mice treated with an A2A antagonist 101 show increased memory (but see 102 )”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [102]
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Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation
Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., & Alberini, C. M. (2011) · Cell · doi:10.1016/j.cell.2011.02.018 · Cited by 1,711
Astrocyte glutamate transport: Review of properties, regulation, and physiological functions
Anderson, C. M., & Swanson, R. A. (2000) · Glia · doi:10.1002/1098-1136(200010)32:1 · Cited by 1,241
Moghaddam, B., & Javitt, D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.181 · Cited by 1,035
Astrocytic Modulation of Sleep Homeostasis and Cognitive Consequences of Sleep Loss
Halassa, M. M., Florian, C., Fellin, T., Munoz, J. R., Lee, S.-Y., Abel, T. G., Haydon, P. G., & Frank, M. G. (2009) · Neuron · doi:10.1016/j.neuron.2008.11.024 · Cited by 877
Animal models of schizophrenia
Jones, C., Watson, D., & Fone, K. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01386.x · Cited by 771
Integrated Brain Circuits: Astrocytic Networks Modulate Neuronal Activity and Behavior
Halassa, M. M., & Haydon, P. G. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135843 · Cited by 763
Fredholm, B. B., Chen, J., Cunha, R. A., Svenningsson, P., & Vaugeois, J. (2005) · International review of neurobiology · doi:10.1016/s0074-7742(05)63007-3 · Cited by 721
Self-citationRoss, C. A., Margolis, R. L., Reading, S. A. J., Pletnikov, M. V., & Coyle, J. T. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.015 · Cited by 719
Cunha, R. A. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(00)00034-6 · Cited by 632
Self-citationHan, J., Kesner, P., Metna-Laurent, M., Duan, T., Xu, L., Georges, F., Koehl, M., Abrous, D. N., Mendizabal-Zubiaga, J., Grandes, P., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.037 · Cited by 514
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Items 101–153 of 153
Chen, L., Wang, J., Xia, M., Sun, L., Sun, J., Gao, L., Zhang, D., & Wu, T. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13979 · Cited by 12
Madeira, D., Lopes, C. R., Simões, A. P., Canas, P. M., Cunha, R. A., & Agostinho, P. M. (2023) · Glia · doi:10.1002/glia.24384 · Cited by 14
Self-citationMadeira, D., Domingues, J., Lopes, C. R., Canas, P. M., Cunha, R. A., & Agostinho, P. M. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04983-6 · Cited by 16
Self-citationNot just neurons: The diverse cellular landscape of learning and memory
Alberini, C. M. (2025) · Neuron · doi:10.1016/j.neuron.2025.05.005 · Cited by 13
Aberrant adenosine signaling in patients with focal cortical dysplasia
Guo, M., Zhang, J., Wang, J., Wang, X., Gao, Q., Tang, C., Deng, J., Xiong, Z., Kong, X., Guan, Y., et al. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03351-6 · Cited by 13
Self-citationLopes, C. R., Silva, A. C., Silva, H. B. L., Canas, P. M., Agostinho, P. M., Cunha, R. A., & Lopes, J. P. (2023) · Biomolecules · doi:10.3390/biom13081173 · Cited by 13
Self-citationAdenosine A2A receptor and glia
Gao, Z. (2023) · International review of neurobiology · doi:10.1016/bs.irn.2023.08.002 · Cited by 14
Wydra, K., Suder, A., Frankowska, M., Borroto‐Escuela, D. O., Fuxé, K., & Filip, M. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5072-8 · Cited by 14
Launay, A., Carvalho, K., Génin, A., Gauvrit, T., Nobili, P., Gómez‐Murcia, V., Augustin, E., Burgard, A., Gambi, J., Fourmy, D., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03115-9 · Cited by 15
Purinergic modulation of glutamate transmission: An expanding role in stress-linked neuropathology
Mayhew, J., Graham, B. A., Biber, K. P. H., Nilsson, M., & Walker, F. R. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.06.023 · Cited by 13
Regulation of Extracellular Adenosine
Boison, D. (2018) · Springer eBooks · doi:10.1007/978-3-319-90808-3_2 · Cited by 12
Self-citationKarati, D., Mukherjee, S., & Roy, S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03441-5 · Cited by 11
Huang, B., Liang, S., Li, X., Xie, Z., Yang, R., Sun, B., Xue, J., Li, B., Wang, S., Shi, H., et al. (2023) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110915 · Cited by 11
Ni, T., Sun, Y., Li, Z., Tan, T., Han, W., Li, M., Zhu, L., Xiao, J., Wang, H., Zhang, W., et al. (2024) · Advanced Science · doi:10.1002/advs.202407628 · Cited by 10
Szczepanik, J. C., de Oliveira, P. A., de Oliveira, J., Mack, J. M., Engel, D. F., Rial, D., Moreira, E. L. G., Bem, A. F. D., & Prediger, R. D. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12544 · Cited by 10
Yang, L., Roy, K., Ioka, S., Otani, R., Amezawa, M., Ishikawa, Y., Chérasse, Y., Kaushik, M. K., Klewe-Nebenius, D., Zhou, L., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1138666 · Cited by 9
Developmental role of adenosine kinase for the expression of sex-dependent neuropsychiatric behavior
Osborne, D. M., Sandau, U. S., Jones, A., Velden, J. W. V., Weingarten, A., Etesami, N. S., Huo, Y., Shen, H., & Boison, D. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.08.025 · Cited by 9
Self-citationCognitive disorders: Potential astrocyte-based mechanism
Li, S., Chen, Y., & Chen, G. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.111181 · Cited by 9
Effects of adenosine A2A receptors on cognitive function in health and disease
Garcia, C. P., Licht-Murava, A., & Orr, A. G. (2023) · International review of neurobiology · doi:10.1016/bs.irn.2023.04.006 · Cited by 8
Glial Purinergic Signaling‐Mediated Oxidative Stress (GPOS) in Neuropsychiatric Disorders
Huang, L., Tang, Y., & Sperlágh, B. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1075440 · Cited by 9
Glutamate, a Key for Astrocytes to Participate in Brain Function and Diseases
Gao, K., & Yu, A. C. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04418-7 · Cited by 10
Purinergic modulation of pathways associated to suicidal behavior
Gonçalves, M. C. B., Corrêa-Velloso, J. C., Naaldijk, Y., Cheffer, A., & Ulrich, H. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0088-3 · Cited by 7
Ma, C., Wu, Y., Liu, X., He, Y., Jia, Y., Chen, P., Yin, D., Ning, Y., Xing, G., Sun, Z., et al. (2021) · Neural Plasticity · doi:10.1155/2021/8812362 · Cited by 7
Adenosine A2A signaling in mood disorders: How far have we come?
Bevilacqua, L. M., Neto, F. D. S., & Kaster, M. P. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.08.006 · Cited by 7
Shalaby, H. N., Zaki, H. F., Ain-Shoka, A. A., & Mohammed, R. A. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02977-2 · Cited by 6
Verkhratsky, A., & Butt, A. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821565-4.00009-2 · Cited by 5
Yang, J., Wang, Y., Xia, Y., Ren, Y., Wang, Z., Meng, X., Li, S., Liu, X., & Shao, J. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04109-9 · Cited by 5
Self-citationGliotransmission at Tripartite Synapses
González-Arias, C., & Perea, G. (2019) · Springer series in computational neuroscience · doi:10.1007/978-3-030-00817-8_8 · Cited by 4
Neuropathological Background of MK-801 for Inducing Murine Model of Schizophrenia
Murueta‐Goyena, A., Odrioizola, A. B., Gargiulo, P. Á., & Lafuente, J. V. (2017) · Springer eBooks · doi:10.1007/978-3-319-53126-7_25 · Cited by 3
MDMA related neuro-inflammation and adenosine receptors
Kermanian, F., Seghatoleslam, M., & Mahakizadeh, S. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2021.105275 · Cited by 4
A2AR antagonist treatment for multiple sclerosis: Current progress and future prospects
Qi, C.-X., Feng, Y., Jiang, Y., Chen, W., Vakal, S., Chen, J., & Zheng, W. (2023) · International review of neurobiology · doi:10.1016/bs.irn.2023.05.012 · Cited by 3
Self-citation[A Review of the State of Purinergic Signaling and Psychological Stress].
Ren, W., & Tang, Y. (2021) · PubMed Central · doi:10.12182/20210160102 · Cited by 3
Gomes, A. L. T., Teixeira-Silva, B., Thomasi, B. B. D. M., Trindade, P., Espírito‐Santo, S., Faria‐Melibeu, A. D. C., Serfaty, C. A., & Campello‐Costa, P. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114427 · Cited by 3
Ye, H., Wan, Y., Wang, X., Wang, S., Zhao, X., Wang, X., Yu, T., Yan, C., Tian, X., Chen, Z., et al. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70038 · Cited by 6
Yang, J., Yang, J., Hu, H., Jiang, W., Zhang, X., Wang, G., Zhao, F., Liao, Y., & Jin, Y. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.119322 · Cited by 2
Adenosine detection technologies: recent advances and applications in the central nervous system
Liao, Y., Jing, J., Jin, W., Tian, X., Peng, T., Zhang, L., & Yuan, Q. (2025) · Sensors & Diagnostics · doi:10.1039/d5sd00170f · Cited by 2
El‐Moaty, H. I. A., Sameh, A., Saber, S., Hamad, R. S., Elmorsy, E. A., Alsoqih, N. S., Farrag, A. A. M., Eissa, H., El-kott, A. F., Negm, S., et al. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103389 · Cited by 2
Adenosine receptors as emerging therapeutic targets in epilepsy
Mal’tseva, V. N., Gaidin, S. G., & Kosenkov, A. M. (2026) · Reviews in the Neurosciences · doi:10.1515/revneuro-2025-0121 · Cited by 4
Mechanisms of Vagus Nerve Stimulation for Epilepsy and Associated Comorbidities
Gao, Q., & Luan, G. (2017) · Neuropsychiatry · doi:10.4172/neuropsychiatry.1000s1003 · Cited by 2
The Adenosine Receptor: A Homeostatic Neuromodulator for Fine-Tuning Control of Cognition
Chen, J. (2018) · Springer eBooks · doi:10.1007/978-3-319-90808-3_15 · Cited by 2
Self-citationSánchez-Florentino, Z. A., Romero-Martínez, B. S., Flores‐Soto, E., Serrano, H., Montaño, L., Valdés‐Tovar, M., Calixto, E., Aquino‐Gálvez, A., López-Riquelme, G. O., Alvarado, R., et al. (2023) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2023.5331 · Cited by 2
Neuropharmacological targets for schizophrenia treatment: An update
de Lima, C. A. C., Barbosa, M. E. O., de Souza-Júnior, F. J. C., Farias, S. V., Fontes-Júnior, E. A., & Maia, C. D. S. F. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111580 · Cited by 1
Dias, L., Ferreira, S. G., Nabais, A. M., Silva, J., Cunha, R. A., & Agostinho, P. M. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70450 · Cited by 1
Self-citationSouza, J. R., Lima‐Silveira, L., Accorsi‐Mendonça, D., & Machado, B. H. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.11.010 · Cited by 1
Ye, H., Wan, Y., Wang, X., Wang, S., Zhao, X., Wang, X., Yu, T., Yan, C., Chen, Z., & Liu, X. (2024) · Research Square · doi:10.21203/rs.3.rs-3878760/v1 · Cited by 1
Astrocytic A2A receptors: Novel targets to manage brain disorders
Henriques, V. J., Gonçalves, N., Agostinho, P. M., & Cunha, R. A. (2017) · Porto Biomedical Journal · doi:10.1016/j.pbj.2017.07.011
Self-citationZhou, X. (2018) · D-Scholarship@Pitt (University of Pittsburgh)
Astrocytic regulation of learning and memory
Park, H., Kim, J. S., & Kim, H. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00060-2
Astrocytic Receptor Systems of the Basal Ganglia
Tushevski, A., Happe, L., Stocco, E., De, R., Macchi, V., Porzionato, A., & Emmi, A. (2025) · Receptors · doi:10.3390/receptors5010002
Istradefylline-Induced Psychosis: What Is the Role of Adenosine?
Tran, T. V., Grossman, L., & Hamrick, E. (2025) · Journal of the Academy of Consultation-Liaison Psychiatry · doi:10.1016/j.jaclp.2025.12.005
Zheng, X., Liu, L., Niu, Z., Li, Y., Liu, Z., Shu, X., Wang, H., Xu, B., Wang, Y., Chen, J., et al. (2026) · Poultry Science · doi:10.1016/j.psj.2026.107232
Self-citationBarros, C. A., Rangel, J. G., Cruz, B. D. O., de Araújo, L. P., & Galdino, G. (2026) · Purinergic Signalling · doi:10.1007/s11302-026-10167-1
Metadata
- Authors
- Matos, M., Shen, H.-Y., Augusto, E., Wang, Y., Wei, C. J., Wang, Y. T., Agostinho, P., Boison, D., Cunha, R. A., & Chen, J.-F.
- Affiliations
- Boston University (US)
- Centro de Neurociências e Biologia Celular (PT)
- Corresponding author
- Chen, Jiang-Fan
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 78
- Issue
- 11
- Pages
- 763-774
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4714966
- OpenAlex
- W2125008776
- Cited by
- 153
- References
- 70
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 12 · 2023: 26 · 2022: 17 · 2021: 8 · 2020: 7 · 2019: 15 · 2018: 18 · 2017: 14 · 2016: 13 · 2015: 5
- FWCI
- 13.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute of Health (NS041083-11, NS073947, MH083973)
- Defense Advanced Research Projects Agency (09-68-ESR-FP-010, W911NF-10-1-0059)
- Portuguese Foundation for Science and Technology (PTDC/SAU-NSC/122254/2010)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- adenosine A2A receptor, astrocytes, glutamate homeostasis, schizophrenia, NMDA receptor NR2B, AMPA receptor internalization, working memory, nucleus accumbens, astrocyte-neuron communication, glutamatergic signaling
- MeSH terms
- Animals, Astrocytes, Cognition Disorders, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Homeostasis, Kainic Acid, Locomotion, Mice, Inbred C57BL, Mice, Transgenic, Psychomotor Disorders, Pyrimidines, Synaptosomes, Time Factors, Triazoles, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, Glutamic Acid, Excitatory Amino Acid Transporter 2, Receptor, Adenosine A2A, Mice
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