PXD046944

PXD046944 is an original dataset announced via ProteomeXchange.

Title	NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine
Description	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 amenable for studying the neurobiology of schizophrenia may contribute to fill the gaps led 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 resective 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.
HostingRepository	PRIDE
AnnounceDate	2024-02-06
AnnouncementXML	Submission_2024-02-06_06:34:50.213.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD046944
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Guilherme Reis-de-Oliveira
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	SYNAPT G2-Si

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-14 04:04:54	ID requested
⏵ 1	2024-02-06 06:34:50	announced

10.6019/PXD046944;

submitter keyword: NMDAr hypofunction, haloperidol,Schizophrenia, antipsychotics, organotypic culture, clozapine

Daniel Martins-de-Souza
contact affiliation	Laboratory of Neuroproteomics, DBBT, IB, Universidade Estadual de Campinas, Brazil
contact email	dmsouza@unicamp.br
lab head
Guilherme Reis-de-Oliveira
contact affiliation	University of Campinas
contact email	guioliveirareis@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046944
     1. Label: PRIDE project
     2. Name: NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine