ArticleJournal of neuroinflammation2018
Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
What it found
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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
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis.BMC infectious diseases · 2022Pooled it
- Occupational Lead Exposure and Brain Tumors: Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2020Pooled it
- Targeting the microglial phosphatidylethanolamine synthesis pathway promotes GABARAP-associated phagocytosis and Aβ clearance in Alzheimer's disease.Signal transduction and targeted therapy · 2026Article
- Dimethyl fumarate ameliorates quinolinic acid-induced ageing and neurodegeneration in Caenorhabditis elegans.Biogerontology · 2026Article
- Tryptophan's Journey Through Pregnancy: The Role of Serotonin.International journal of tryptophan research : IJTR · 2026Review
- Endocrine-disrupting properties of heavy metal exposure contribute to the intergenerational effects on learning and memory.Frontiers in endocrinology · 2026Review
- Kynurenine Pathway Metabolites as Mediators of Exercise-Induced Mood Enhancement, Fatigue Resistance, and Neuroprotection.International journal of molecular sciences · 2025Review
- Production, Mechanisms, and Therapeutic Strategies of Tryptophan Metabolites in CNS Diseases.Molecular neurobiology · 2025Review
- Review
- Glutamate-Mediated Neural Alterations in Lead Exposure: Mechanisms, Pathways, and Phenotypes.Toxics · 2025Review
- Diverse Physiological Roles of Kynurenine Pathway Metabolites: Updated Implications for Health and Disease.Metabolites · 2025Review
- Tryptophan Metabolism in Alzheimer's Disease with the Involvement of Microglia and Astrocyte Crosstalk and Gut-Brain Axis.Aging and disease · 2024Review
- Avicularin Attenuated Lead-Induced Ferroptosis, Neuroinflammation, and Memory Impairment in Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics.Neurochemical research · 2023Review
- The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases.International journal of molecular sciences · 2023Review
- Butyrate ameliorates quinolinic acid-induced cognitive decline in obesity models.The Journal of clinical investigation · 2023Article
- Seasonal Changes in Serum Metabolites in Multiple Sclerosis Relapse.International journal of molecular sciences · 2023Article
- An emerging role for microglia in stress-effects on memory.The European journal of neuroscience · 2022Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both Pb and QA impair spatial learning and memory. Pb activates astrocytes and microglia, which in turn induce the synthesis of QA. We hypothesized increased QA production in response to Pb exposure as a novel mechanism of Pb-neurotoxicity.
methodsTwo experimental paradigms were used. In experiment one, Wistar rat pups were exposed to Pb via their dams' drinking water from postnatal day 1 to 21. Control group was given regular water. In the second protocol, QA (9 mM) or normal saline (as Vehicle Control) was infused into right lateral ventricle of 21-day old rats for 7 days using osmotic pumps. Learning and memory were assessed by Morris water maze test on postnatal day 30 or 45 in both Pb- and QA-exposed rats. QA levels in the Pb exposed rats were measured in blood by ELISA and in the brain by immunohistochemistry on postnatal days 45 and 60. Expression of various molecules involved in learning and memory was analyzed by Western blot. Means of control and experimental groups were compared with two-way repeated measure ANOVA (learning) and t test (all other variables).
resultsPb exposure increased QA level in the blood (by ~ 58%) and increased (p < 0.05) the number of QA-immunoreactive cells in the cortex, and CA1, CA3 and dentate gyrus regions of the hippocampus, compared to control rats. In separate experiments, QA infusion impaired learning and short-term memory similar to Pb. PSD-95, PP1, and PP2A were decreased (p < 0.05) in the QA-infused rats, whereas tau phosphorylation was increased, compared to vehicle infused rats.
conclusionPutting together the results of the two experimental paradigms, we propose that increased QA production in response to Pb exposure is a novel mechanism of Pb-induced neurotoxicity.
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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.