title: Altered functional protein networks in the prefrontal cortex and amygdala of victims of suicide.
abstract: Probing molecular brain mechanisms related to increased suicide risk is an important issue in biological psychiatry research. Gene expression studies on post mortem brains indicate extensive changes prior to a successful suicide attempt; however, proteomic studies are scarce. Thus, we performed a DIGE proteomic analysis of post mortem tissue samples from the prefrontal cortex and amygdala of suicide victims to identify protein changes and biomarker candidates of suicide. Among our matched spots we found 46 and 16 significant differences in the prefrontal cortex and amygdala, respectively; by using the industry standard t test and 1.3 fold change as cut off for significance. Because of the risk of false discoveries (FDR) in these data, we also made FDR adjustment by calculating the q-values for all the t tests performed and by using 0.06 and 0.4 as alpha thresholds we reduced the number of significant spots to 27 and 9 respectively. From these we identified 59 proteins in the cortex and 11 proteins in the amygdala. These proteins are related to biological functions and structures such as metabolism, the redox system, the cytoskeleton, synaptic function, and proteolysis. Thirteen of these proteins (CBR1, DPYSL2, EFHD2, FKBP4, GFAP, GLUL, HSPA8, NEFL, NEFM, PGAM1, PRDX6, SELENBP1 and VIM,) have already been suggested to be biomarkers of psychiatric disorders at protein or genome level. We also pointed out 9 proteins that changed in both the amygdala and the cortex, and from these, GFAP, INA, NEFL, NEFM and TUBA1 are interacting cytoskeletal proteins that have a functional connection to glutamate, GABA, and serotonin receptors. Moreover, ACTB, CTSD and GFAP displayed opposite changes in the two examined brain structures that might be a suitable characteristic for brain imaging studies. The opposite changes of ACTB, CTSD and GFAP in the two brain structures were validated by western blot analysis.
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest, Hungary. kakekesi@dec001.geobio.elte.hu
authors.forename: Katalin Adrienna
authors.initials: KA
authors.lastname: Kékesi
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.forename: Attila
authors.initials: A
authors.lastname: Simor
authors.forename: Péter
authors.initials: P
authors.lastname: Gulyássy
authors.forename: Eva Mónika
authors.initials: EM
authors.lastname: Szegő
authors.forename: Eva
authors.initials: E
authors.lastname: Hunyadi-Gulyás
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Darula
authors.forename: Katalin F
authors.initials: KF
authors.lastname: Medzihradszky
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: András
authors.initials: A
authors.lastname: Czurkó
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000378:metabolism*; D001344:Autopsy; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D003599:Cytoskeleton / Q000378:metabolism; D016208:Databases, Factual; D005189:False Positive Reactions; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D017397:Prefrontal Cortex / Q000378:metabolism*; D020033:Protein Isoforms; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D013405:Suicide
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D010455:Peptides; D020033:Protein Isoforms