Molecular mapping of striatal subdivisions in juvenile Macaca Mulata

Abstract

The striatum of the primate brain can be subdivided into three distinct anatomical subregions: caudate (CAU), putamen (PUT), and ventral striatum (VS). Although these subregions share several anatomical connections, cell morphological, and histochemical features, they differ considerably in their vulnerability to different neurological and psychiatric diseases, and these brain regions have significantly different functions in health and disease. In order to better understand the molecular underpinnings of the different disease and functional vulnerabilities, transcriptional profiles were generated from the CAU, PUT, and VS of five juvenile rhesus macaques (Macaca mulatta) using human cDNA neuromicroarrays containing triplicate spots of 1227 cDNAs. Differences in microarray gene expression were assessed using z score analysis and 1.5-fold change between paired subregions. Clustering of genes based on dissimilarity of expression patterns between regions revealed subregion specific expression profiles encoding Gprotein-coupled receptor signaling transcripts, transcription factors, kinases and phosphatases, and cell signaling and signal transduction transcripts. Twelve transcripts were examined using quantitative real-time PCR (qPCR), and 81% demonstrated alterations similar to those seen with microarray analysis, some of which were statistically significant. Subregion specific transcription profiles support the anatomical differentiation and potential disease vulnerabilities of the respective subregions.