PXD046944 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-11-14 04:04:54 | ID requested | |
⏵ 1 | 2024-02-06 06:34:50 | announced | |
Publication List
Keyword List
submitter keyword: NMDAr hypofunction, haloperidol,Schizophrenia, antipsychotics, organotypic culture, clozapine |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046944
- Label: PRIDE project
- Name: NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine