ArticleThe Journal of clinical investigation2012
Adenosine augmentation ameliorates psychotic and cognitive endophenotypes of schizophrenia.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Innovative Strategies to Enhance the Bioavailability of Cannabidiol: Nanotechnology and Advanced Delivery Systems.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Adenosine receptors and acute kidney injury: perspectives for future therapy.Purinergic signalling · 2025Review
- Exploring the Sensitivity of Peripheral ADA Levels Measurement in Establishing Psychosis Susceptibility.Journal of molecular neuroscience : MN · 2025Article
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Bipolar mania and epilepsy pathophysiology and treatment may converge in purine metabolism: A new perspective on available evidence.Neuropharmacology · 2023Review
- Downregulation of the glucose transporter GLUT 1 in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice.Journal of neuroinflammation · 2023Article
- The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks.Frontiers in cellular neuroscience · 2023Review
- Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation.Gastroenterology · 2023Article
- Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?International journal of molecular sciences · 2022Review
- Adenosine Receptors in Neuropsychiatric Disorders: Fine Regulators of Neurotransmission and Potential Therapeutic Targets.International journal of molecular sciences · 2022Review
- Spontaneous Adenosine and Dopamine Cotransmission in the Caudate-Putamen Is Regulated by Adenosine Receptors.ACS chemical neuroscience · 2021Article
- Targeting purinergic receptors to suppress the cytokine storm induced by SARS-CoV-2 infection in pulmonary tissue.International immunopharmacology · 2021Review
- ATP and adenosine-Two players in the control of seizures and epilepsy development.Progress in neurobiology · 2021Review
- Adenosine kinase: An epigenetic modulator in development and disease.Neurochemistry international · 2021Review
- Adenosine and Kynurenic Acid Interactions: Possible Relevance for Schizophrenia Treatment?Frontiers in pharmacology · 2021Article
- The Good, the Bad, and the Deadly: Adenosinergic Mechanisms Underlying Sudden Unexpected Death in Epilepsy.Frontiers in neuroscience · 2021Review
- Specialty Grand Challenge for Brain Disease Mechanisms.Frontiers in molecular neuroscience · 2021Article
- Adenosine ATranslational stroke research · 2020Article
- Epigenetics and epilepsy prevention: The therapeutic potential of adenosine and metabolic therapies.Neuropharmacology · 2020Review
- Adenosine Kinase Expression in the Frontal Cortex in Schizophrenia.Schizophrenia bulletin · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
An emerging theory of schizophrenia postulates that hypofunction of adenosine signaling may contribute to its pathophysiology. This study was designed to test the "adenosine hypothesis" of schizophrenia and to evaluate focal adenosine-based strategies for therapy. We found that augmentation of adenosine by pharmacologic inhibition of adenosine kinase (ADK), the key enzyme of adenosine clearance, exerted antipsychotic-like activity in mice. Further, overexpression of ADK in transgenic mice was associated with attentional impairments linked to schizophrenia. We observed that the striatal adenosine A2A receptor links adenosine tone and psychomotor response to amphetamine, an indicator of dopaminergic signaling. Finally, intrastriatal implants of engineered adenosine-releasing cells restored the locomotor response to amphetamine in mice overexpressing ADK, whereas the same grafts placed proximal to the hippocampus of transgenic mice reversed their working memory deficit. This functional double dissociation between striatal and hippocampal adenosine demonstrated in Adk transgenic mice highlights the independent contributions of these two interconnected brain regions in the pathophysiology of schizophrenia and thus provides the rationale for developing local adenosine augmentation therapies for the treatment of schizophrenia.
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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.