ArticleNeuropharmacology2015
Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia.
Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies.European archives of psychiatry and clinical neuroscience · 2023Pooled it
- Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2017Pooled it
- Tryptophan challenge in individuals with schizophrenia and healthy controls: acute effects on circulating kynurenine and kynurenic acid, cognition and cerebral blood flow.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Targeting the SIRT6-TDO2/KYNA-mTOR axis rescues synaptic and cognitive deficits in fetal growth restriction offspring.Experimental & molecular medicine · 2026Article
- Kynurenic Acid Synthesis from D-Kynurenine in the Cerebellum: A Distinct Role of D-Amino Acid Oxidase.Cells · 2025Article
- Functional Impairments in Learning and Signal Propagation Following Prenatal Kynurenine Treatment in Mice.The European journal of neuroscience · 2025Article
- Parental kynurenine 3-monooxygenase genotype in mice directs sex-specific behavioral outcomes in offspring.Biology of sex differences · 2025Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- Article
- Review
- Kynurenine aminotransferase II inhibition promotes sleep and rescues impairments induced by neurodevelopmental insult.Translational psychiatry · 2023Article
- Potential diagnostic biomarkers for schizophrenia.Medical review (2021) · 2022Review
- Article
- Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence.Frontiers in psychiatry · 2022Article
- Learning Deficits Induced by High-Calorie Feeding in the Rat are Associated With Impaired Brain Kynurenine Pathway Metabolism.International journal of tryptophan research : IJTR · 2022Article
- A single prenatal lipopolysaccharide injection has acute, but not long-lasting, effects on cerebral kynurenine pathway metabolism in mice.The European journal of neuroscience · 2021Article
- SubchronicAntioxidants (Basel, Switzerland) · 2021Article
- Time of Day-Dependent Alterations in Hippocampal Kynurenic Acid, Glutamate, and GABA in Adult Rats Exposed to Elevated Kynurenic Acid During Neurodevelopment.Frontiers in psychiatry · 2021Article
- The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites.International journal of tryptophan research : IJTR · 2021Article
- Gut Biofactory-Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review.Nutrients · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing kynurenine (100 mg/day; progeny = EKYNs) from ED15 until ED22. Controls were fed an unadulterated mash (progeny = ECONs). The dietary loading procedure elevated maternal and fetal plasma kynurenine (2223% and 693% above controls, respectively) and increased fetal KYNA (forebrain; 500% above controls) on ED21. Elevations in forebrain KYNA disappeared after termination of the loading (PD2), but KYNA levels in the prefrontal cortex (PFC) were unexpectedly increased again when measured in adults (PD56-80; 75% above controls). We also observed changes in several markers of prefrontal excitability, including expression of the α7nAChR (22% and 17% reductions at PD2 and PD56-80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56-80), dendritic spine density (11-14% decrease at PD56-80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ.
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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.