NMDA glutamate receptor antagonist MK ‐801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine
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Le résumé fourni par la source
Deciphering the molecular pathways associated with N-methyl-D-aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain-derived models that are amenable to studying the neurobiology of schizophrenia may contribute to filling the gaps left by the widely employed animal models. Here, we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK-801 on human brain slice cultures obtained from adult donors submitted to respective neurosurgery. Initially, we demonstrated that MK-801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass-spectrometry-based proteomics and systems biology in silico analyses, we found that MK-801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology, including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid, and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK-801-induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset, we identified potential modulators of the MK-801-induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia. This dataset is publicly available and may be helpful in further studies aimed at evaluating the effects of MK-801 and antipsychotics in the human brain.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <scp>NMDA</scp> glutamate receptor antagonist <scp>MK</scp> ‐801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine
- Date Crossref
- 08/02/2024
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Universidade Estadual de Campinas (UNICAMP) pays non établi dans la noticeUniversité ou école supérieure
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Universidade de São Paulo pays non établi dans la noticeUniversité ou école supérieure
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Conselho Nacional de Desenvolvimento Científico e Tecnológico pays non établi dans la noticeOrganisme public
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D’Or Institute for Research and Education pays non établi dans la noticeOrganisation à but non lucratif
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Institute of Biology University of Campinas (UNICAMP) Campinas Brazil Laboratory of Neuroproteomics pays non établi dans la noticeUniversité ou école supérieure
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Ribeirao Preto Medical School University of Sao Paulo Sao Paulo Brazil Department of Biochemistry and Immunology pays non établi dans la noticeUniversité ou école supérieure
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Experimental Medicine Research Cluster (EMRC) University of Campinas Campinas Sao Paulo Brazil pays non établi dans la noticeUniversité ou école supérieure
Universidade Estadual de Campinas (UNICAMP), Universidade de São Paulo et Conselho Nacional de Desenvolvimento Científico e Tecnológico, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.