Human iN neuronal model of schizophrenia displays dysregulation of chromogranin B and related neuropeptide transmitter signatures
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Le résumé fourni par la source
Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of neurotransmitters released to mediate cell-cell communication which are essential to brain functions in health and disease. We hypothesized that SZ may involve dysregulation of neurotransmitters secreted from neurons. To gain an understanding of human SZ, induced neurons (iNs) were derived from SZ patients and healthy control subjects to investigate peptide neurotransmitters, known as neuropeptides, which represent the major class of transmitters. The iNs were subjected to depolarization by high KCl in the culture medium and the secreted neuropeptides were identified and quantitated by nano-LC-MS/MS tandem mass spectrometry. Several neuropeptides were identified from schizophrenia patient-derived neurons, including chromogranin B (CHGB), neurotensin, and natriuretic peptide. Focusing on the main secreted CHGB neuropeptides, results revealed differences in SZ iNs compared to control iN neurons. Lower numbers of distinct CHGB peptides were found in the SZ secretion media compared to controls. Mapping of the peptides to the CHGB precursor revealed peptides unique to either SZ or control, and peptides common to both conditions. Also, the iNs secreted neuropeptides under both KCl and basal (no KCl) conditions. These findings are consistent with reports that chromogranin B levels are reduced in the cerebrospinal fluid and specific brain regions of SZ patients. These findings suggest that iNs derived from SZ patients can model the decreased CHGB neuropeptides observed in human SZ.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Human iN neuronal model of schizophrenia displays dysregulation of chromogranin B and related neuropeptide transmitter signatures
- Date Crossref
- 02/02/2024
- Éditeur
- Springer Science and Business Media LLC
- 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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University of California San Diego Department of Psychiatry pays non établi dans la noticeUniversité ou école supérieure
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Salk Institute for Biological Studies pays non établi dans la noticeOrganisation à but non lucratif
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VA San Diego Healthcare System pays non établi dans la noticeÉtablissement de santé
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Research Network (United States) pays non établi dans la noticeEntreprise
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University of Montana pays non établi dans la noticeUniversité ou école supérieure
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Skaggs School of Pharmacy and Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Desert-Pacific Mental Illness Research Education and Clinical Center pays non établi dans la noticeÉtablissement de santé
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Global Research Network on Social Determinants of Health pays non établi dans la noticeInstitution
Department of Psychiatry — University of California San Diego, Salk Institute for Biological Studies et VA San Diego Healthcare System, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.