Learning and memory are among higher-order cognitive functions that are based on numerous molecular processes including changes in the expression of genes. To identify genes associated with learning and memory formation, here, we used the RNA-seq (high-throughput mRNA sequencing) technology to compare hippocampal transcriptomes between mice with high and low Morris water maze (MWM) cognitive performance. We identified 88 differentially expressed genes (DEGs) and 24 differentially alternatively spliced transcripts between the high- and low-MWM-performance mice. Although the sets of DEGs and differentially alternatively spliced transcripts did not overlap, both were found to be enriched with genes related to the same type of biological processes: trans-synaptic signaling, cognition, and glutamatergic transmission. These findings were supported by the results of weighted-gene co-expression network analysis (WGCNA) revealing the enrichment of MWM-cognitive-performance-correlating gene modules with very similar Gene Ontology terms. High-MWM-performance mice manifested mostly higher expression of the genes associated with glutamatergic transmission and long-term potentiation implementation, which are processes necessary for memory acquisition and consolidation. In this set, there were genes participating in the regulation of trans-synaptic signaling, primarily AMPA receptor signaling (Nrn1, Nptx1, Homer3, Prkce, Napa, Camk2b, Syt7, and Nrgn) and calcium turnover (Hpca, Caln1, Orai2, Cpne4, and Cpne9). In high-MWM-performance mice, we also demonstrated significant upregulation of the “flip” splice variant of Gria1 and Gria2 transcripts encoding subunits of AMPA receptor. Altogether, our data helped to identify specific genes in the hippocampus that are associated with learning and long-term memory. We hypothesized that the differences in MWM cognitive performance between the mouse groups are linked with increased long-term potentiation, which is mainly mediated by increased glutamatergic transmission, primarily AMPA receptor signaling.
Background/Aim: We previously have described the "3+1" tumors cure approach consisting of individual time schedule of cyclophosphamide and dsDNA preparation administrations. The aim of the study was to adapt the "3+1" approach based on eradication of cancer stem cells to the model of murine ascitic cyclophosphamide-resistant lymphosarcoma (RLS). Materials and Methods: Adaptation of the "3+1" approach includes the identification of the timing to disrupt the tumorigenic potential of a certain tumor. Results: The proposed therapeutic scheme allowed complete reduction of primary RLS ascites in experimental animals. However, reduction of primary ascites due to the complementary action of cyclophosphamide and dsDNA was inevitably followed by the development of a secondary one, most likely arising from a solid carcinomatous formation in the peritoneal wall. Conclusion: The "3+1" approach resulted in the elimination of cancer stem cells, and, as a consequence, in the complete reduction of RLS ascites.Malignant neoplasms rank second in the world after cardiovascular disorders in overall mortality rates. Recent studies indicate a much higher complexity of the disease than previously thought. The main characteristic of this complexity determining the unpredictable response of neoplasms to a variety of therapeutic procedures and the difficulties in their cure is the heterogeneity of malignant cells that include a subpopulation of almost "indestructible" cells, which possess an incredible survival and proliferative potency, and is designated as tumor-initiating stem cells or cancer stem cells (CSCs) (1, 2).The main hallmarks of cancer stem cells are their capabilities of (1) self-renewal in through unlimited replicative cycles, (2) producing a progeny of committed cells with high proliferative activity, but incapable of inducing a new tumor, and (3) retaining a potency to induce new tumors with similar histological properties in a series of transplantations (3). CSCs possess a number of features allowing their dominance in co-existence with organism: self-sufficiency in proliferative stimuli (4), reduced sensitivity to anti-proliferative ones (5), immortalization (6, 7), dedifferentiation (8), genomic instability (9), increased efflux and metabolism of xenobiotics (10, 11), reversed "Warburg effect" (12, 13), suppression of pro-apoptotic signals ( 14), as well as stimulation of pathways causing apoptosis evasion (15). Another essential for disease development property of CSCs is their migratory capacity, allowing exit into the bloodstream, and formation of new growth foci in distant organs (16)(17)(18)(19)(20). Thus, the aforementioned properties of CSCs are such that they create 795
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