Evidence map›Paper›PMID 38789891›Full record

ArticlePharmacological reports : PR2024

Prenatal MAM exposure raises kynurenic acid levels in the prefrontal cortex of adult rats.

Francesca Frescura, Tibor Stark, Edoardo Tiziani, Serena Di Martino, Jana Ruda-Kucerova, Filippo Drago, Luca Ferraro, Vincenzo Micale, Sarah Beggiato

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Article in Pharmacological reports : PR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Francesca FrescuraDepartment of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121, Ferrara, Italy.
Tibor StarkDepartment Emotion Research, Max Planck Institute of Psychiatry, 80807, Munich, Germany.
Edoardo TizianiDepartment of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121, Ferrara, Italy.ORCID http://orcid.org/0000-0002-9303-0561
Serena Di MartinoDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.
Jana Ruda-KucerovaDepartment of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.ORCID http://orcid.org/0000-0002-1846-0799
Filippo DragoDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.ORCID http://orcid.org/0000-0003-2887-5223
Luca FerraroDepartment of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121, Ferrara, Italy. luca.ferraro@unife.it.ORCID http://orcid.org/0000-0003-2390-6414
Vincenzo Micale *Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.ORCID http://orcid.org/0000-0002-6232-8859
Sarah Beggiato *Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121, Ferrara, Italy.ORCID http://orcid.org/0000-0002-8826-7556

Funding

FAR2023 2023Partnership for Research and Innovation in the Mediterranean Area Project no. PE00000006
6 · The paper itself

Abstract

backgroundElevated brain levels of kynurenic acid (KYNA), a metabolite in the kynurenine pathway, are associated with cognitive dysfunctions, which are nowadays often considered as fundamental characteristics of several psychopathologies; however, the role of KYNA in mental illnesses, such as schizophrenia, is not fully elucidated. This study aimed to assess KYNA levels in the prefrontal cortex (PFC) of rats prenatally treated with methylazoxymethanol (MAM) acetate, i.e., a well-validated neurodevelopmental animal model of schizophrenia. The effects of an early pharmacological modulation of the endogenous cannabinoid system were also evaluated.

methodsPregnant Sprague-Dawley rats were treated with MAM (22 mg/kg, ip) or its vehicle at gestational day 17. Male offspring were treated with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day, ip) or with the typical antipsychotic haloperidol (0.6 mg/kg/day, ip) from postnatal day (PND) 19 to PND39. The locomotor activity and cognitive performance were assessed in the novel object recognition test and the open field test in adulthood. KYNA levels in the PFC of prenatally MAM-treated rats were also assessed.

resultsA significant cognitive impairment was observed in prenatally MAM-treated rats (p < 0.01), which was associated with enhanced PFC KYNA levels (p < 0.05). The peripubertal AM251, but not haloperidol, treatment ameliorated the cognitive deficit (p < 0.05), by normalizing the PFC KYNA content in MAM rats.

conclusionsThe present findings suggest that the cognitive deficit observed in MAM rats may be related to enhanced PFC KYNA levels which could be, in turn, mediated by the activation of cannabinoid CB1 receptor. These results further support the modulation of brain KYNA levels as a potential therapeutic strategy to ameliorate the cognitive dysfunctions in schizophrenia.

Indexed as

Kynurenic AcidMethylazoxymethanol AcetatePrefrontal CortexPrenatal Exposure Delayed EffectsRats, Sprague-DawleySchizophreniaAnimalsAntipsychotic AgentsCognitive DysfunctionDisease Models, AnimalFemaleHaloperidolMalePiperidinesPregnancyPyrazolesAM 251Antipsychotic AgentsHaloperidolKynurenic AcidMethylazoxymethanol AcetatePiperidinesPyrazolesReceptor, Cannabinoid, CB1AM251HaloperidolKynurenine PathwayNovel object recognition testPeripubertal treatmentSchizophrenia

Identifiers

PMID38789891

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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.