Comparative proteomic analysis with postmortem prefrontal cortex tissues of suicide victims versus controls.
BACKGROUND
The origin of suicidal behaviour is multifactorial including genetic, neurobiological and psychosocial correlates. Although there is no doubt that serotonin has a central role, the overall genetic findings with candidate genes of the serotonergic pathway are relatively inconsistent and suggests that other, yet unidentified, genes and gene products are also contributing to the vulnerability of suicidality. Proteomics is a powerful method to investigate modifications in protein expression.


METHODS
We performed comparative proteomic analysis with prefrontal cortex tissues of 17 suicide victims and 9 controls.


RESULTS
Applying two dimensional gel electrophoresis and image analysis we detected five protein spots to differ significantly in intensities between both groups. Three of them appeared only in suicide victims and could be identified by means of MALDI-TOF-MS analysis and protein database search as alpha crystallin chain B (CRYAB), glial fibrillary acidic protein (GFAP) and manganese superoxide dismutase (SOD2). CRYAB belongs to the low molecular heat shock proteins and GFAP is known as a marker of astrocytic activation in gliosis. SOD2 is a major antioxidant enzyme protecting cells against oxidative injury. Two further spots revealed higher intensities in the control group but had no unambiguous protein to match.


CONCLUSIONS
Our findings suggest that proteins, being involved in glial function, neurodegeneration and oxidative stress neuronal injury, might also have an impact upon the neurobiological cascade leading to suicidality. As animal data provide evidence for an up-regulation of GFAP synthesis in astrocytes due to alterations in 5-HT levels, similar mechanisms of interaction might also be relevant in humans.
Schlicht
Katja
K
Psychiatric Hospital of the Ludwig-Maximilians-University, Munich, Nussbaumstrasse 7, D-80336 Munich, Germany. ecoccaro@yoda.bsd.uchicago.edu
Büttner
Andreas
A
Siedler
Frank
F
Scheffer
Bea
B
Zill
Peter
P
Eisenmenger
Wolfgang
W
Ackenheil
Manfred
M
Bondy
Brigitta
B
D000293:Adolescent; D000328:Adult; D002102:Cadaver; D002648:Child; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology*; D040901:Proteomics / Q000379:methods*; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013405:Suicide; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D005904:Glial Fibrillary Acidic Protein; D012701:Serotonin; D013482:Superoxide Dismutase; D038203:alpha-Crystallin B Chain; D000099156:Superoxide Dismutase 2