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| Author(s): |
Giuliana da Silva Zuccoli
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2024-09-30 |
| Examining board members: |
Daniel Martins de Souza;
Marcelo Bispo de Jesus;
Paulo Dalgalarrondo;
Carolina Demarchi Munhoz;
Andrea da Silva Torrão
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| Advisor: | Daniel Martins de Souza |
| Abstract | |
Schizophrenia is a severe psychiatric disorder that can affect up to 1% of the world’s population and usually manifests itself at the end of adolescence/beginning of adult life. According to the neurodevelopment hypothesis, early dysfunctions in the developing brain, due to genetic and environmental factors, lead to the appearance of schizophrenia. Studies conducted with the purpose of elucidating the mechanisms of the disorder show that important cellular processes are altered, such as mitochondrial function, response to reactive oxygen species and others. To stablish if there are alterations related to energy metabolism and mitochondrial functions in early stages of neurodevelopment and their possible implications to the stablishment of schizophrenia, in the present work the mitochondrial and nuclear proteomes of neural stem cells (NSCs) and neurons derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients and healthy controls were analyzed. The comparative analysis was conducted through large-scale mass spectrometry-based proteomics. Subsequently, the proteins found to be significantly different in schizophrenia when compared to controls were submitted to an in silico systems biology analysis to obtain the biochemical pathways related to each condition. Cellular processes and canonical pathways related to mitochondrial function, cell-cycle control, DNA repair and neuritogenesis were found altered in schizophrenia revealing that key processes of neurodevelopment may be affected, such as neuronal differentiation and axonal guidance, and give rise to the phenotypic alterations observed in adult patients. In this way, the data generated in this dissertation will contribute to the identification of mechanisms that can potentially be altered during neurodevelopment in schizophrenia patients and contribute to a better understanding of the disorder’s stablishmen (AU) | |
| FAPESP's process: | 18/14666-4 - Influence of the endocannabinoid system on the energetic profile of neural cells during neurodevelopment: implications in Schizophrenia |
| Grantee: | Giuliana da Silva Zuccoli |
| Support Opportunities: | Scholarships in Brazil - Doctorate |