GROWTH-ASSOCIATED PROTEIN (GAP-43), ITS MESSENGER-RNA, AND PROTEIN-KINASE-C (PKC) ISOENZYMES IN BRAIN-REGIONS OF DEPRESSED SUICIDES

The aim of this study was to investigate whether the previously observ ed adaptive changes in the monoaminergic receptors in post-mortem brai ns of depressed suicide victims are associated with alteration in some functional proteins involved in serotonergic neuronal signalling, nam ely 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 b y Western blotting with monoclonal antibodies specific for these prote ins. 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 front opolar 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 o f GAP-43 in the establishment and reorganization of synaptic connectio ns, the finding of selective reduction of this protein in prefrontal c ortex suggests that a dysfunctional synaptic organization in this regi on may be associated with depression and suicidal behaviour. This stud y provides the first evidence of an alteration in a protein related to the neuronal plasticity in the brain of depressed suicide victims.