Mitochondrial, cell cycle control and neuritogenesis alterations in an iPSC-based neurodevelopmental model for schizophrenia.

Autor: Zuccoli GS; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil., Nascimento JM; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; D'Or Institute for Research and Education (IDOR), São Paulo, Brazil., Moraes-Vieira PM; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, SP, 13083-862, Brazil.; Obesity and Comorbidities Research Center (OCRC), University of Campinas, São Paulo, Brazil., Rehen SK; D'Or Institute for Research and Education (IDOR), São Paulo, Brazil.; Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Martins-de-Souza D; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil. dmsouza@unicamp.br.; D'Or Institute for Research and Education (IDOR), São Paulo, Brazil. dmsouza@unicamp.br.; Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, SP, 13083-862, Brazil. dmsouza@unicamp.br.; Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, Brazil. dmsouza@unicamp.br.
Jazyk: angličtina
Zdroj: European archives of psychiatry and clinical neuroscience [Eur Arch Psychiatry Clin Neurosci] 2023 Dec; Vol. 273 (8), pp. 1649-1664. Date of Electronic Publication: 2023 Apr 11.
DOI: 10.1007/s00406-023-01605-x
Abstrakt: Schizophrenia is a severe psychiatric disorder of neurodevelopmental origin that affects around 1% of the world's population. Proteomic studies and other approaches have provided evidence of compromised cellular processes in the disorder, including mitochondrial function. Most of the studies so far have been conducted on postmortem brain tissue from patients, and therefore, do not allow the evaluation of the neurodevelopmental aspect of the disorder. To circumvent that, we studied the mitochondrial and nuclear proteomes of neural stem cells (NSCs) and neurons derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients versus healthy controls to assess possible alterations related to energy metabolism and mitochondrial function during neurodevelopment in the disorder. Our results revealed differentially expressed proteins in pathways related to mitochondrial function, cell cycle control, DNA repair and neuritogenesis and their possible implication in key process of neurodevelopment, such as neuronal differentiation and axonal guidance signaling. Moreover, functional analysis of NSCs revealed alterations in mitochondrial oxygen consumption in schizophrenia-derived cells and a tendency of higher levels of intracellular reactive oxygen species (ROS). Hence, this study shows evidence that alterations in important cellular processes are present during neurodevelopment and could be involved with the establishment of schizophrenia, as well as the phenotypic traits observed in adult patients. Neural stem cells (NSCs) and neurons were derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients and controls. Proteomic analyses were performed on the enriched mitochondrial and nuclear fractions of NSCs and neurons. Whole-cell proteomic analysis was also performed in neurons. Our results revealed alteration in proteins related to mitochondrial function, cell cycle control, among others. We also performed energy pathway analysis and reactive oxygen species (ROS) analysis of NSCs, which revealed alterations in mitochondrial oxygen consumption and a tendency of higher levels of intracellular ROS in schizophrenia-derived cells.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
Databáze: MEDLINE
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