Expression of the myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) in the prefrontal cortex and hippocampus ofsuicide victims

Background: Although suicide is a leading cause of death in the United Stat es and represents a significant public health threat, little is known about the neurobiological or molecular factors that contribute to its pathophysi ology. A number of studies now indicate that lithium has considerable effic acy in the prevention of suicide in patients with affective disorders, and accumulating evidence indicates that protein kinase C (PKC) and its substra tes, in particular the myristoylated alanine-rich C kinase substrate (MARCK S), are primary targets of chronic lithium treatment. We therefore hypothes ized that a dysregulation in MARCKS expression in key brain regions could c ontribute to the pathophysiology associated with suicide. To address this, we examined MARCKS, as well as the closely related MARCKS-related protein ( MRP), mRNA expression in the hippocampus and dorsolateral prefrontal cortex of suicide victims and normal controls. Method: MARCKS and MRP mRNA expres sion was assessed by quantitative in situ hybridization histochemistry perf ormed on postmortem hippocampal and dorsolateral prefrontal cortex sections from suicide (N = 9) and normal control (N = 10) brains. Results: In the n ormal hippocampus, both MARCKS and MRP mRNA expression were highest in the granule cell layer and low-moderate in CA1, CA3, and hilus. A high level of MRP mRNA expression was also observed in the white matter of the fimbria/f ornix. Neither MARCKS nor MRP mRNA expression levels differed significantly in the granule cell layer, CA3, hilus, or CAI in suicide victims relative to normal controls (I-way ANOVA, p > .05). In the normal prefrontal cortex, MARCKS was expressed exclusively in gray matter (layers I-VI), whereas MRP was expressed in both gray and white matter. Neither MARCKS nor MRP mRNA e xpression levels in the gray and white matter regions of the dorsal prefron tal cortex differed between suicides and normal controls (l-way ANOVA, p >. 05). Conclusion: The present findings are the first to demonstrate the expr ession and distribution of MARCKS and MRP in the human hippocampus and dors olateral prefrontal cortex, and their expression pattern within these regio ns bears strong resemblance to those observed in the adult rat brain. Compa rison of MARCKS and MRP mRNA expression in the hippocampus and prefrontal c ortex of suicide victims and normal controls indicates that these 2 mRNAs a re not differentially regulated in these regions. However, differences in M ARCKS and MRP protein expression and function cannot be ruled out by the pr esent findings.