Transport Phenomena in the Nervous System: Physiological and Pathological Aspects

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Although Foster did not distinguish himself in research, his laboratory produced many of the leading physiologists of the late 19th century in Great Britain and the United States. In Foster wrote a major book Textbook of Physiology , which passed through seven editions and was translated into German, Italian, and Russian.

He also published Lectures on the History of Physiology In , partly in response to increased opposition in England to experimentation with animals, Foster was instrumental in founding the Physiological Society, the first organization of professional physiologists. The American tradition drew also on the continental schools. Bowditch , who worked with Carl Ludwig, joined Martin to organize the American Physiological Society in , and in the society sponsored publication of the American Journal of Physiology. Physiological chemistry followed a course partly independent of physiology. The American tradition in physiological chemistry initially followed that in Germany; in England, however, it developed from a Cambridge laboratory founded in to complement the physical approach started earlier by Foster.

Physiology in the 20th century was a mature science; during a century of growth , physiology became the parent of a number of related disciplines , of which biochemistry , biophysics , general physiology, and molecular biology are the most vigorous examples.

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Physiology, however, retains an important position among the functional sciences that are closely related to the field of medicine. Although many research areas, especially in mammalian physiology, have been fully exploited from a classical- organ and organ-system point of view, comparative studies in physiology may be expected to continue. The solution of the major unsolved problems of physiology will require technical and expensive research by teams of specialized investigators.

Unsolved problems include the unravelling of the ultimate bases of the phenomena of life. Research in physiology also is aimed at the integration of the varied activities of cells , tissues, and organs at the level of the intact organism. Both analytical and integrative approaches uncover new problems that also must be solved. In many instances, the solution is of practical value in medicine or helps to improve the understanding of both human beings and other animals.

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Appears unread. Clean, bright and tight. They are formed during the late stage of apoptosis and contain nuclear material, cellular organelles and membrane contents. They express phosphatidylserine on their surface and have a permeable membrane Turturici et al. Apoptotic bodies tend to elicit an anti-inflammatory or tolerogenic response when taken up by neighboring cells Lai et al. TABLE 1. The properties of different types of extracellular vesicles EVs. Extracellular vesicles are composed of various molecules including proteins, lipids, and nucleic acids.

Secreted proteins participate in intercellular communication and play a role in cell signaling, differentiation, cell adhesion, angiogenesis, and apoptosis. A variety of cytokines, chemokines, growth factors, extracellular matrix ECM proteins and remodeling enzymes have been identified in MSCs derived from different sources and their secretomes Kupcova Skalnikova, Kim et al. Lai et al. E1 line by high performance liquid chromatography. In these two articles we can find a common subset of proteins Supplementary Tables S1 and S2.

Among the sets of proteins, in addition to cytoplasmic proteins a remarkable number of membrane proteins have been found. The proteins located in the plasma membrane and cytoplasm are more commonly sorted into EVs compared with the proteins in the nucleus and mitochondria of different cell types Yoon et al.

Specific markers of MSCs, i. Consistent with the previous finding that EVs proteome include the proteins associated with EVs biogenesis and trafficking. Proteins implicated in intracellular transport and fusion, i. RAB proteins are accompanied with granule secretion, Golgi apparatus transport, tight junctions formation and ligand sequestration at the plasma membrane. These proteins, i. Some of these molecules were also characterized by Thery et al.

Nowadays, there are two public databases: EVpedia and ExoCarta containing data of EVs components of different cell types from several studies Mathivanan et al. Similar to exosomes from other sources, protein components in MSC-derived exosomes do not remain constant due to heterogeneity of MSCs. Moreover, variations in the cell preparation have an influence on secretome profile of MSC derived from different sources Lavoie and Rosu-Myles, The proteomic analysis of EVs derived from MSCs isolated from different sources reveals distinguishing features from EVs derived from other types of cells Skalnikova et al.

However, the functional differences between EVs originated from distinct MSC sources clearly indicate the existence of difference in their composition. From all mentioned vesicles only MenSC -exosomes are able to enhance neurit outgrowth in cortical neuron cultures, while Cho-SC-exosomes cause even decrease of total neuron branch number.

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Moreover BM- and MenSC-derived exosomes increased the rate of neuritic growth in dorsal root ganglia neurons culture in comparison to control cells Lopez-Verrilli et al. Similar observations were made in case of glioblastoma research. Furthermore these functional differences have been demonstrated even between vesicles from the same source but belonging to other sub-populations. Exosome-enriched fraction derived from BM-MSCs enhanced neurite outgrowth whereas the microvesicle-enriched fraction showed inhibitory effect Lopez-Verrilli et al.

The realization of more comparative studies between EVs derived from MSC from different sources is required. In literature we can find a few examples of proteins which were present in microvesicles although they were not detected in cells of their origin. Authors of these articles associate this phenomenon with existence of very precise proteins sorting system during microvesicles biogenesis or limitation of protein identification techniques Table 2 which very often suffer from high detection threshold or necessity of normalization of obtained results to the total protein level.

TABLE 2. Examples of articles with identification of differences between proteins composition in cells and vesicles originated from them.

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  • Except proteins EVs contain bioactive lipids. As for proteins, the lipid composition in EVs is distinct from that of the cell origin. Internal membranes of EVs isolated from different cell types are enriched in lysobisphosphatidic acids that modulate budding process and lipids associated with lipid rafts such as cholesterol, ceramide, sphingolipids, and glycerophospholipids with saturated fatty-acyl chains Urbanelli et al.

    Sphingomyelin and cholesterol allow the tight packing of lipid bilayers and increase rigidity and stability of EVs derived from different cells, prevent their recognition by blood components and uptake, facilitate the fusion of EVs Yoon et al. EVs also contain many lipid mediators such as prostaglandins and enzymes involved in their synthesis from membrane phospholipids.

    Also a large panel of free fatty acids including arachidonic acid were detected in EVs from mast cells Subra et al. There were found profound discrepancies between the exosomal and cellular content of miRNA suggesting an active process of sorting and packaging of miRNA into exosomes Zhang J. MSC-derived exosomes also contain significant amount of transfer RNA tRNA , with striking differences in content between cells of AT or bone marrow origin, while no difference in miRNA content between these two cell sources has been found Baglio et al.

    This may account for the differences observed between them Muhammad et al. Such process was observed in cancer-derived EVs and processed RNA was toxic for primary human cells Chakrabortty et al. The high interest in RNA cargo of exosomes takes advantage of new methods of RNA isolation, which may bring more detailed characterization in near future Enderle et al.

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    Extracellular vesicles released from parental cells may be broken down, thus releasing their content into extracellular space or neighbor cells may internalize them. The pathways through which EVs enter target cells impact EV-mediated biomolecule delivery. Several types of interactions between EVs and target cells have been demonstrated.