Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8473
Authors: Frankenfeld, Antonia Marie
Title: Proteomic analysis of human cerebrospinal fluid of patients with major depressive disorder and schizophrenia
Other Title: Proteomische Analyse humanen Liquor cerebrospinalis von Proband:innen mit Depressionen und Schizophrenie
Online publication date: 15-Dec-2022
Year of first publication: 2022
Language: english
Abstract: Herein, we report a proteomic investigation of CSF samples taken from depressed and schizophrenic patients and healthy controls resulting in the identification of a total of 277 proteins. Since the proteome is a dynamic system that reflects the current state and environment of an organism, alterations on protein level were explored in order to achieve a better understanding of the pathophysiology behind the mental disorders. Sixty-six proteins were found to be differently abundant in the comparison SCZ versus healthy individuals and 25 proteins in the comparison MDD versus CTRL. All altered proteins except for APO2 appeared to be downregulated in disease. This study verifies altered expression levels of 11 proteins that have been presented in previous studies. These 11 proteins, namely AGT, ALDOA, COL6A1, CPE, NPTX1, NPTXR, NRXN3, OPCML, PAM, SERPINF1 and SERPINI1, may be potential biomarkers for MDD disease. Moreover, 14 proteins were observed to be differently expressed in MDD for the first time. These potential biomarker candidates need to be investigated further in the future. In SCZ cohort, 19 differently abundant proteins were identified that have been discussed as potential biomarkers for SCZ in previous studies (A2M, APOA2, APOE, APP, C5, CFH, CLSTN1, CNDP1, COL6A1, GC, IGHA1, ITIH1, ITIH2, ITIH4, LSAMP, NFASC, PLG, SERPINI1 and SIRPA). However, the findings regarding up and downregulations are partly conflicting suggesting that the molecular diversity and the expression on proteomic level is even more complex than the variation in clinical symptoms. Extensive research under consideration of the administered medication is inevitable for progress in this field. Furthermore, 47 differently abundant proteins were determined that may be involved in SCZ pathophysiology and which to our knowledge have not been observed to be altered in previous studies. Mental disorders share some clinical manifestations indicating that the pathophysiology behind the diseases is partly alike. This assumption is supported by the shared alterations in expression levels of some proteins in SCZ and MDD. It thus becomes clear that the complexity of mental disorders may require a set of biomarkers (biosignature) rather than single altered proteins as markers for future diagnostic and treatment. Further validation of the proteins found to be altered in the present study is of great interest. To avoid technical errors a larger patient cohort and a division of patients according to their symptoms and age is advisable. Also, the analysis of drug naïve patients enables a better understanding of the manifestation of mental disorders on proteomic level. The findings prove the employment of 1DE gel and capillary-LC-ESI-MS to be a reliable and solid method for the analysis of CSF. At the same time, this study presents an alternative method for proteomic analysis which enabled the detection of about 86.6% of the proteins detected with 1DE gel and LC-ESI-MS. This method, in-solution technique combined with nano-LC-ESI-MS/MS, is less time consuming and fewer preparation steps minimize the sources of technical errors. Moreover, samples can be analysed individually which opens new perspectives; for example, a comparison of differences in expression levels between the sexes becomes possible. In the SCZ cohort seven proteins were identified that showed differences in expression correlating with gender (SHANK2, C5, IGHA1, IGFBP7, ANKRD36C, LGALS3BP, PLEKHH2) of which two had also been observed to be downregulated in SCZ cohort compared to control. Even though only a small number of samples were analysed employing in-solution and nano-LC MS we can state that this method is an excellent alternative to the 1DE gel approach. In addition, it proves that the field of proteomics is rapidly improving in view of technology and that highly sensitive tools are available these days for the investigation of dynamic body fluids. This study provides numerous proteins that are possibly related to the mental disorders SCZ and MDD and which have a great potential to contribute to the diagnostic and treatment of these diseases in the future.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-8473
URN: urn:nbn:de:hebis:77-openscience-51f15a1d-21b1-4624-9894-9f5d3ead384c0
Version: Original work
Publication type: Dissertation
License: In Copyright
Information on rights of use: http://rightsstatements.org/vocab/InC/1.0/
Extent: IX, 74 Seiten ; Illustrationen, Diagramme
Appears in collections:JGU-Publikationen

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