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| Author(s): |
Helena Passarelli Giroud Joaquim
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2018-02-02 |
| Examining board members: |
Wagner Farid Gattaz;
Orestes Vicente Forlenza;
Paulo Clemente Sallet;
Silvio Marques Zanata
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| Advisor: | Wagner Farid Gattaz |
| Abstract | |
Schizophrenia is a mulfatorial psychiatric disorder that affects about 1% of the world\'s population. Despite considerable progress in recent years, the etiology of the disease has not yet been elucidated mainly because the heterogeneity of disease onset and progression. Often the symptoms overlap to other neuropsychiatric disorders, which turns difficult to differentiate through essentially clinical methods. The researchers have focused in identify mesureable molecular characteristics that can help to elucidate schizophrenia etiology. There are already important findings regarding markers in the brain, but recent efforts have focused on finding peripheral biomarkers. This study aimed to find a protein profile in platelets of schizophrenia drug-naïve patients. For comparision we recruited two more groups: healthy controls and psychiatric control. We used two complementary proteomic approaches for analysis: a classic tool using two-dimensional electrophoresis with subsequent identification of the spots by mass spectrometry; and a large-scale label-free shotgun identification approach. The sample comprised 11 schizophrenic patients, 8 patients with mood disorders (psychiatric control and 16 healthy controls. 2-DE profiles of each sample were generated in triplicate. 110 proteins spots were identified in most gels of control group, 83 in most gels of schizophrenia group, and 80 proteins spots in most gels of bipolar disorder patients. Among these proteins spots, 76 were common to all three groups; 5 to controls and schizophrenia group; 2 common to controls and bipolar disorders groups; 2 exclusive of bipolar disorder patients and 27 proteins spots were identified exclusively in the control group. The 27 exclusive protein spots of control group were identified by LC-MS/MS. Proteins related to neurotransmission, synapse, neurodevelopment, cellular homeostasis, calcium signaling, apoptosis, immune response, and oxidative stress were identified. To verify the results, we chose proteins according to their function already described in the literature and novelty in platelets and first onset psychosis patients research. By western blotting we verified the difference in levels of annexin A3 and peroxiredoxin 6 between groups, but not of glutathione S-transferase pi 1 or 78-kDa glucose-regulated protein. Both proteins differentially expressed have already been related to phospholipase A2, which is the main enzyme responsible for the membrane phospholipids metabolism and has been associated with neuropsychiatric disorders, including schizophrenia. Despite the good and promising results presented and published, there are still some analytical and bioinformatic approaches to be performed in search for candidates for platelet schizophrenia biomarkers. The data from shotgun approach require further analysis, as well as verification and validation in larger cohorts. The sample enrroled in this study is greatly important and certainly informed us much about the proteomic alterations still in the first onset psychosis (AU) | |
| FAPESP's process: | 13/10350-9 - Proteomics of schizophrenia: the search for biomarkers in platelets |
| Grantee: | Helena Passarelli Giroud Joaquim Nadal |
| Support Opportunities: | Scholarships in Brazil - Doctorate |