Expression of the Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) and MARCKS-Related Protein (MRP) in the Prefrontal Cortex and Hippocampus of Suicide Victims

Background: Although suicide is a leading cause of death in the United States and represents a significant public health threat, little is known about the neurobiological or molecular factors that contributeto its pathophysiology. A number of studies now indicate that lithium has considerable efficacyin the prevention of suicide in patients with affective disorders, and accumulating evidence indicatesthat protein kinase C (PKC) and its substrates, in particular the myristoylated alanine-rich C kinasesubstrate (MARCKS), are primary targets of chronic lithium treatment. We therefore hypothesizedthat a dysregulation in MARCKS expression in key brain regions could contribute to the pathophysiologyassociated with suicide. To address this, we examined MARCKS, as well as the closely relatedMARCKS-related protein (MRP), mRNA expression in the hippocampus and dorsolateral prefrontalcortex of suicide victims and normal controls. Method: MARCKS and MRP mRNA expression was assessed by quantitative in situ hybridization histochemistry performed on postmortem hippocampaland dorsolateral prefrontal cortex sections from suicide (N = 9) and normal control (N = 10) brains.Results: In the normal hippocampus, both MARCKS and MRP mRNA expression were highest in thegranule cell layer and low-moderate in CA1, CA3, and hilus. A high level of MRP mRNA expressionwas also observed in the white matter of the fimbria/fornix. Neither MARCKS nor MRP mRNA expressionlevels differed significantly in the granule cell layer, CA3, hilus, or CA1 in suicide victimsrelative to normal controls (1-way ANOVA, p > .05). In the normal prefrontal cortex, MARCKS wasexpressed exclusively in gray matter (layers I-VI), whereas MRP was expressed in both gray andwhite matter. Neither MARCKS nor MRP mRNA expression levels in the gray and white matter regionsof the dorsal prefrontal cortex differed between suicides and normal controls (1-way ANOVA,p > .05). Conclusion: The present findings are the first to demonstrate the expression and distribution of MARCKS and MRP in the human hippocampus and dorsolateral prefrontal cortex, and their expressionpattern within these regions bears strong resemblance to those observed in the adult rat brain.Comparison of MARCKS and MRP mRNA expression in the hippocampus and prefrontal cortex ofsuicide victims and normal controls indicates that these 2 mRNAs are not differentially regulated inthese regions. However, differences in MARCKS and MRP protein expression and function cannot beruled out by the present findings.