ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2010
Reduction of endogenous kynurenic acid formation enhances extracellular glutamate, hippocampal plasticity, and cognitive behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
144 citing papers in PubMed, 2 syntheses or guidelines pooled it, 229 citations in OpenAlex.
- Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review.Journal of psychopharmacology (Oxford, England) · 2021Pooled it
- Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2017Pooled it
- Targeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene.Biological psychiatry · 2019Trial
- Targeting inflammation to influence cognitive function following spinal cord injury: a randomized clinical trial.Spinal cord · 2017Trial
- Emerging links between gut dysbiosis, aryl hydrocarbon receptor activation, and Parkinson's disease.Communications biology · 2026Review
- The role of the kynurenine pathway in the pathogenesis of pain and affective disorders after traumatic brain injury.Brain, behavior, & immunity - health · 2026Review
- Dietary Tryptophan Allocation in Depression: Serotonin-Kynurenine Balance, Microbial Indole Pathways, and Inflammatory Phenotypes.Nutrients · 2026Review
- Alpha Frequency Dysrhythmia in Treatment-Resistant Schizophrenia: Associations with EEG Background Changes, Disorganized Symptoms, and Dissociation.Biomedicines · 2026Article
- Targeting the SIRT6-TDO2/KYNA-mTOR axis rescues synaptic and cognitive deficits in fetal growth restriction offspring.Experimental & molecular medicine · 2026Article
- Fasting and Caloric Restriction Activate an ADIOL-NHR-91-Kynurenine Pathway Signaling Axis to Promote Healthspan.Aging cell · 2026Article
- Biochemical and Pharmacological Studies on Kynurenic Acid Metabolism in theBiomolecules · 2026Article
- Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress.Journal of neuroinflammation · 2026Review
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers.Current topics in medicinal chemistry · 2026Review
- Review
- Article
- Interactions between gut microbiota and parkinson's disease: the role of tryptophan metabolism.Cell communication and signaling : CCS · 2025Review
- Procognitive effects of methyl 2-amino-3-methoxybenzoate (or daopine) may involve the dorsal striatal anthranilic acid pathway and mutimetabolite-multitarget pharmacology.Behavioural pharmacology · 2025Article
- Kynurenic Acid Synthesis from D-Kynurenine in the Cerebellum: A Distinct Role of D-Amino Acid Oxidase.Cells · 2025Article
- The Power Struggle: Kynurenine Pathway Enzyme Knockouts and Brain Mitochondrial Respiration.Journal of neurochemistry · 2025Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
At endogenous brain concentrations, the astrocyte-derived metabolite kynurenic acid (KYNA) antagonizes the alpha 7 nicotinic acetylcholine receptor and, possibly, the glycine co-agonist site of the NMDA receptor. The functions of these two receptors, which are intimately involved in synaptic plasticity and cognitive processes, may, therefore, be enhanced by reductions in brain KYNA levels. This concept was tested in mice with a targeted deletion of kynurenine aminotransferase II (KAT II), a major biosynthetic enzyme of brain KYNA. At 21 days of age, KAT II knock-out mice had reduced hippocampal KYNA levels (-71%) and showed significantly increased performance in three cognitive paradigms that rely in part on the integrity of hippocampal function, namely object exploration and recognition, passive avoidance, and spatial discrimination. Moreover, compared with wild-type controls, hippocampal slices from KAT II-deficient mice showed a significant increase in the amplitude of long-term potentiation in vitro. These functional changes were accompanied by reduced extracellular KYNA (-66%) and increased extracellular glutamate (+51%) concentrations, measured by hippocampal microdialysis in vivo. Taken together, a picture emerges in which a reduction in the astrocytic formation of KYNA increases glutamatergic tone in the hippocampus and enhances cognitive abilities and synaptic plasticity. Our studies raise the prospect that interventions aimed specifically at reducing KYNA formation in the brain may constitute a promising molecular strategy for cognitive improvement in health and disease.
Indexed as
Identifiers
What OpenQuestion holds
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.