Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC) isoenzymes in brain regions of depressed suicides.
The aim of this study was to investigate whether the previously observed adaptive changes in the monoaminergic receptors in post-mortem brains of depressed suicide victims are associated with alteration in some functional proteins involved in serotonergic neuronal signalling, namely PKC and GAP-43. Selected regions from ten brains of antidepressant-free depressed suicide victims and ten matched controls were used to examine the levels of GAP-43 protein, GAP-43 mRNA and PKC isoenzymes by Western blotting with monoclonal antibodies specific for these proteins. A major finding of the study was a significant decrease in GAP-43 protein levels and its mRNA expression in prefrontal cortex (BA9) (by 24% and 34%, respectively) of suicide brains compared to controls. No significant changes were found in GAP-43 protein or its mRNA in frontopolar cortex (BA10), amygdala, substantia nigra or putamen. Levels of PKC isoenzymes had a heterogenous regional distribution but were not significantly altered in any of the regions examined. Given the role of GAP-43 in the establishment and reorganization of synaptic connections, the finding of selective reduction of this protein in prefrontal cortex suggests that a dysfunctional synaptic organization in this region may be associated with depression and suicidal behaviour. This study provides the first evidence of an alteration in a protein related to the neuronal plasticity in the brain of depressed suicide victims.
Department of Pharmacology, Royal Ottawa Hospital, Faculty of Medicine, University of Ottawa, Ontario, Canada. phrdina@rohcg.on.ca
P
P
Hrdina
G
G
Faludi
Q
Q
Li
C
C
Bendotti
K
K
Tekes
P
P
Sotonyi
M
M
Palkovits
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D013405:Suicide; D014158:Transcription, Genetic
D019922:GAP-43 Protein; D007527:Isoenzymes; D012333:RNA, Messenger; D011493:Protein Kinase C