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. 2012 Dec;262(8):657-66.
doi: 10.1007/s00406-012-0301-3. Epub 2012 Feb 21.

Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function

Daniel Martins-de-Souza  1 , Paul C Guest, Natacha Vanattou-Saifoudine, Hassan Rahmoune, Sabine Bahn
Affiliations

Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function

Daniel Martins-de-Souza et al. Eur Arch Psychiatry Clin Neurosci. 2012 Dec.

Abstract

There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders. Here, we present a comparative phosphoproteome analysis of postmortem dorsolateral prefrontal cortex tissues from 24 MDD patients and 12 control donors. Tissue extracts were analyzed using liquid chromatography mass spectrometry in a data-independent manner (LC-MS(E)). Our analyses resulted in the identification of 5,195 phosphopeptides, corresponding to 802 non-redundant proteins. Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls, being 20 differentially phosphorylated in at least 2 peptides. The majority of these phosphorylated proteins were associated with synaptic transmission and cellular architecture not only pointing out potential biomarker candidates but mainly shedding light to the comprehension of MDD pathobiology.

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Figures

Fig. 1
Fig. 1
a Biological function and b cellular localization of the differentially phosphorylated proteins in MDD brains
Fig. 2
Fig. 2
Network of proteins interactions among the differentially phosphorylated proteins according to systems biology analyses by ingenuity pathways knowledge base
Fig. 3
Fig. 3
Validation of Dynamin 1 as a candidate of differentially phosphorylated protein in the DLPFC from MDD patients and controls. p values were obtained by Student’s t-test statistical analysis
Fig. 4
Fig. 4
Integrated view of the role players of the synaptic dysfunction in MDD brains. Colored proteins were found differentially phosphorylated between MDD patients versus controls
See this image and copyright information in PMC

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