Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia

Autor: Alfredo Bellon, Vincent Feuillet, Alonso Cortez-Resendiz, Faycal Mouaffak, Lan Kong, L. Elliot Hong, Lilian De Godoy, Therese M. Jay, Anne Hosmalin, Marie-Odile Krebs
Přispěvatelé: Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), EPS Ville-Evrard - Pavillon Provence [Saint-Denis], University of Maryland School of Medicine, University of Maryland System, Baptist Hospital [Miami, FL, USA] (BH), GHU Paris Psychiatrie et Neurosciences, Hosmalin, Anne, Pôle de Psychiatrie d'Adultes 93G04 [Saint-Denis] (PSA93G04), Pôle hospitalo-universitaire d’Evaluation Prévention et Innovation Thérapeutique [Paris] (PEPIT), GHU Paris Psychiatrie & Neurosciences, Martinez Rico, Clara
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Psychiatry
Molecular Psychiatry, 2022, 27 (6), pp.2787-2802. ⟨10.1038/s41380-022-01514-w⟩
Molecular Psychiatry, 2022, Online ahead of print. ⟨10.1038/s41380-022-01514-w⟩
ISSN: 1359-4184
1476-5578
Popis: The long lapse between the presumptive origin of schizophrenia (SCZ) during early development and its diagnosis in late adolescence has hindered the study of crucial neurodevelopmental processes directly in living patients. Dopamine, a neurotransmitter consistently associated with the pathophysiology of SCZ, participates in several aspects of brain development including pruning of neuronal extensions. Excessive pruning is considered the cause of the most consistent finding in SCZ, namely decreased brain volume. It is therefore possible that patients with SCZ carry an increased susceptibility to dopamine’s pruning effects and that this susceptibility would be more obvious in the early stages of neuronal development when dopamine pruning effects appear to be more prominent. Obtaining developing neurons from living patients is not feasible. Instead, we used Monocyte-Derived-Neuronal-like Cells (MDNCs) as these cells can be generated in only 20 days and deliver reproducible results. In this study, we expanded the number of individuals in whom we tested the reproducibility of MDNCs. We also deepened the characterization of MDNCs by comparing its neurostructure to that of human developing neurons. Moreover, we studied MDNCs from 12 controls and 13 patients with SCZ. Patients’ cells differentiate more efficiently, extend longer secondary neurites and grow more primary neurites. In addition, MDNCs from medicated patients expresses less D1R and prune more primary neurites when exposed to dopamine. Haloperidol did not influence our results but the role of other antipsychotics was not examined and thus, needs to be considered as a confounder.
Databáze: OpenAIRE
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