Regulation of gene expression in the postnatally developing hippocampus might contribute to the emergence of selective memory function. gene expression in different cell types. This mechanism is partially conserved across species, and may thus contribute to the similarity of basic hippocampal characteristics across mammals. This mechanism also exhibits a phylogenetic diversity that may contribute to more subtle species differences in hippocampal structure and function observed at the cellular level. Introduction The hippocampal formation is comprised of a group of cortical regions located in the medial temporal lobe, which is essential for spatial and episodic memory functions [1], [2], [3], [4], [5]. Recent data suggest that the gradual emergence of different types of hippocampus-dependent memory processes may be dependent on the differential maturation of distinct hippocampal circuits during early postnatal life [6], and that major changes in gene expression [7] are concomitant with structural changes occurring at different ages in distinct hippocampal regions [6], [8]. Using stringent analysis criteria, we previously identified a number of genes exhibiting differences in expression between distinct hippocampal regions across developmental ages [7]. Darapladib manufacture In the current study, we confirmed the existence of a large group of genes whose expression decreased between birth and six months of age in Darapladib manufacture CA1, and after one year of age in CA3, to reach expression levels observed in 6C12-year-old monkeys. In addition to the previously identified group of genes expressed in astrocytes [7], we found a number of genes expressed in neurons and oligodendrocytes that exhibited similar patterns of expression. We used several bioinformatics tools, including NCBI (National Center for Biotechnology Information), miRBase, TargetScan, microRNA.org and Affymetrix bioinformatics software, to perform predictive analyses and determine possible mechanisms of co-regulation of the expression of hundreds of genes expressed in different cell types. Our analyses Kv2.1 antibody specifically considered the involvement of miRNAs (small RNA molecules acting as post-transcriptional regulatory elements), which have been shown to play a major role in developmental processes [9], [10]. Indeed, previous studies revealed the prominent role of miRNAs in the early stages of neuronal fate determination and differentiation, via the down-regulation of non-neuronal transcripts, thereby helping to establish neuronal cell identity [11], [12]. Involvement of miRNAs in the maturation of post-mitotic neurons has also been demonstrated [13], . Although most previous studies focused on single miRNAs, it is now thought that at least 100 miRNAs present in postmitotic neurons contribute to fine-tuning of dendritic protein levels in response to different patterns of synaptic activation [16]. One final, but very important feature of miRNAs is their ability to be transferred between cells via specific transporters, thus potentially effectuating the regulation of gene expression in neighboring cells [17]. Here, we present experimental genome-wide analyses of Darapladib manufacture gene expression, and predictive bioinformatics analyses, which suggest that miRNAs may Darapladib manufacture contribute to the co-regulation of gene expression in different cell types (i.e., in neurons, astrocytes and oligodendrocytes) at different postnatal ages in distinct regions of the developing monkey hippocampus. Interestingly, sixty-five percent of these predicted miRNAs are conserved across species, from rodents to humans; whereas thirty-five percent are specific to primates, including humans. In addition, we found that some genes exhibiting greater down-regulation of their expression were the predicted targets of a greater number of miRNAs. Materials and Methods Experimental Subjects Sixteen male rhesus monkeys (and and (Figure 2; Table S2). According to miRBase, amongst these 65 miRNAs, 33 miRNAs (51%) are included in miRNA clusters, i.e., grouped in genomic places where they may be vunerable to become co-regulated; 23 miRNAs (35%) are primate-specific; and 18 miRNAs (28%) Darapladib manufacture aren’t contained in clusters and so are not primate particular. We used.