期刊
MOLECULAR PSYCHIATRY
卷 27, 期 6, 页码 2787-2802出版社
SPRINGERNATURE
DOI: 10.1038/s41380-022-01514-w
关键词
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资金
- Penn State College of Medicine, Penn State Hershey Medical Center, Universite Paris Descartes Sorbonne Paris Cite
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- CNRS
- Foundation pour la Recherche Medicale (FRM) [SPF20080511940, FRM DPP 2015 1033966]
- French Government's Investissement d'Avenir program, Laboratoires d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10LABX-62-IBEID]
- Consejo Nacional de Ciencia y Tecnologia (CONACYT) [74641]
- American Psychiatric Association
- Department of Psychiatry and Behavioral Health, Penn State Hershey Medical Center
This study used Monocyte-Derived-Neuronal-like Cells (MDNCs) to investigate the dopamine pruning effects in the neuronal development of schizophrenia (SCZ) patients. The results showed that SCZ patients' cells differentiated more efficiently, extended longer neurites, but had less primary neurites. Additionally, medication in patients influenced the pruning effects under dopamine exposure.
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.
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