ABSTRACT
One of important aspects of development of Alzheimer's disease is degeneration of septal cholinergic neurons that innervate the hippocampus. We took advantage of widely used model of cholinergic deficit in the hippocampus, intracerebroventricular administration of 192IgG-saporin (Ig-saporin), to analyze the postponed consequences of cholinergic deficit in different parts of the hippocampus. We studied effects of the immunotoxin on the behavior of rats and gene expression in the dorsal and ventral hippocampus using RNA-seq approach. We found that under normal conditions dorsal and ventral parts of the hippocampus differ in the expression of 1129 protein-coding genes and 49 non-coding RNAs (ncRNAs) and do not differ in the expression of 10 microRNAs, which were detected in both parts of the hippocampus. Ig-saporin-induced degeneration of cholinergic septal neurons did not affect rat behavior in open field, T-maze, and passive avoidance task but impaired memory retention in Morris water maze. To analyze 192Ig-saporin-induced changes in the gene expression, we formed the following groups of genes: genes expressed exclusively in certain cell types (neurons, astrocytes, microglia, oligodendrocytes, and vascular cells) and, among universally expressed genes, a group of genes that encode ribosome-forming proteins. For all groups of genes, the alterations in the gene expression produced by the immunotoxin were stronger in the dorsal as compared to the ventral hippocampus. We found that, among groups of universally expressed genes, Ig-saporin increased the expression of ribosome-forming proteins in both dorsal and ventral hippocampus. Ig-saporin also strongly upregulated expression of microglia-specific genes only in the dorsal hippocampus. A subset of affected microglial genes comprised genes associated with inflammation, however, did not include genes related to acute inflammation such as interleukins-1b, -6, -15, and -18 as well as TNF. The expression of other cell-specific genes (genes specific for neurons, astrocytes, oligodendrocytes, and vascular cells) was unaffected. The data obtained suggest that disturbance of memory-associated behavior after administration of Ig-saporin is associated with upregulation of microglia-associated genes in the dorsal but not ventral hippocampus.
ABSTRACT
The European healthcare system is characterized by different kinds of funding: public, insurance-based, and mixed. In Italy, the prolonged economic crisis and the need for a cost reduction in the public administrations make necessary a cut in expenditure, which has a significant impact also on the funding of the healthcare system. The comparison of different European healthcare systems may offer useful insights for a better definition of the European and / or national healthcare provision strategies, which would be economically and financially sustainable but also capable to protect the population health. In this regard, it is worth to analyze the Russian healthcare system, which in the last years has undergone significant changes in its structure and in the way healthcare services are supplied. The peculiarity of the Russian healthcare system, which is quite different from the European standards for both professional requirements and theoretical knowledge, makes Russia an absolutely interesting partner for a future joint venture research. This paper describes the Russian national healthcare system highlights the differences in the demographic and socio-economic structures relatively to the Italian model. The paper supports a reflection on the sustainability of the health care systems and on the organizational forms that would guarantee the supply of better healthcare services in terms of quality, appropriateness and safety, compatibly with its economic sustainability.
