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| Author(s): |
Daniel Martins de Souza
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: | 2008-03-19 |
| Examining board members: |
Emmanuel Dias Neto;
Gilberto Barbosa Domont;
Francesco Langone;
Gonçalo Amarante Guimarães Pereira;
Paulo Clemente Sallet
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| Advisor: | Emmanuel Dias Neto |
| Abstract | |
Schizophrenia is a mental debilitating disorder that affects 1% of the world population. It is characterized by positives symptoms such as delirium and hallucinations and negative symptoms such as apathy and emotion decrease. Here, we have studied the ranscriptome and proteome of brain samples of patients with schizophrenia, in an attempt to identify genes and proteins markers of the disease. Our transcriptome analyses of pre-frontal cortex were performed with Serial Analysis of Gene Expression (SAGE), here used for the first time in the study of schizophrenia. The data obtained allowed the analysis of approximately 20,000 transcripts, which suggested the importance of myelinization, synaptic function, energy metabolism and calcium homeostasis, in the genesis of schizophrenia. A series of genes previously implicated in the disease were identified, together with new potential markers which were revealed here for the first time. A small fraction of these was validated using realtime PCR, which confirmed some of the SAGE findings. Two-dimensional gel electrophoresis, mass spectrometry and shotgun proteomics were the approaches used here for large-scale protein analysis in schizophrenia. These approaches were used in brain samples derived from distinct areas such as pre-frontal cortex and anterior temporal lobe, and indicated quanitative alterations of proteins involved with calcium homeostasis, energy and oligodendrocyte metabolism and cytoskeleton. In general, a good correlation was observed when the different approaches (transcriptome and proteome) were used. In may cases, the alterations of some genes was not reflected by a correspondent alteration of the encoded protein. However, in most cases, reproducible alterations were found in the same pathways. Beside the identification of new schizophrenia-related genes and proteins, we also confirmed the the differential regulation of oligodendrocyte, synaptic and energetic metabolism, in this disease.Our data reinforce previous findings, and suggest new potential biomarkers that may contribute to the understanding of schizophrenia (AU) | |