Background: Although suicide is a leading cause of death in the United States represents a significant public health threat, little is known about the neurobiological or molecular factors that contribute to its pathophysiology. A number of studies now indicate that lithium has considerable efficacy in the prevention of suicide in patients with affective disorders, accumulating evidence indicates that protein kinase C (PKC) its substrates, in particular the myristoylated alanine-rich C kinase substrate (MARCKS), are primary targets of chronic lithium treatment. We therefore hypothesized that a dysregulation in MARCKS expression in key brain regions could contribute 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 dorsolateral prefrontal cortex of suicide victims normal controls. Method: MARCKS MRP mRNA expression was assessed by quantitative in situ hybridization histochemistry performed on postmortem hippocampal and dorsolateral prefrontal cortex sections from suicide (N = 9) normal control (N = 10) brains. Results: In the normal hippocampus, both MARCKS MRP mRNA expression were highest in the granule cell layer low-moderate in CA1, CA3, hilus. A high level of MRP mRNA expression was also observed in the white matter of the fimbria/fornix. Neither MARCKS nor MRP mRNA expression levels differed significantly in the granule cell layer, CA3, hilus, or CA1 in suicide victims relative to normal controls (1- 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 white matter. Neither MARCKS nor MRP mRNA expression levels in the gray white matter regions of the dorsal prefrontal cortex differed between suicides normal controls (1-way ANOVA, p > .05). Conclusion: The present findings are the first to demonstrate the expression distribution of MARCKS MRP in the human hippocampus dorsolateral prefrontal cortex, their expression pattern within these regions bears strong resemblance to those observed in the adult rat brain. Comparison of MARCKS MRP mRNA expression in the hippocampus prefrontal cortex of suicide victims normal controls indicates that these 2 mRNAs are not differentially regulated in these regions. However, differences in MARCKS MRP protein expression function cannot be ruled out by the present findings.
|Number of pages
|Journal of Clinical Psychiatry
|Published - Mar 8 1999
ASJC Scopus subject areas
- Psychiatry and Mental health