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

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    Author
    Bellon, Alfredo
    Feuillet, Vincent
    Cortez-Resendiz, Alonso
    Mouaffak, Faycal
    Kong, Lan
    Hong, L Elliot
    De Godoy, Lilian
    Jay, Therese M
    Hosmalin, Anne
    Krebs, Marie-Odile
    Date
    2022-04-01
    Journal
    Molecular Psychiatry
    Publisher
    Springer Nature
    Type
    Article
    
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    See at
    https://doi.org/10.1038/s41380-022-01514-w
    Abstract
    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. © 2022, The Author(s).
    Rights/Terms
    © 2022. The Author(s).
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18573
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41380-022-01514-w
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