[Features of the in vitro expression profile of hippocampal neurogenic niche cells during optogenetic stimulation]. / Osobennosti ékspressionnogo profilia kletok v modeli neirogennoi nishi gippokampa in vitro pri optogeneticheskoi stimuliatsii.

In the central nervous system of mammals, there are specialized areas in which neurogenesis - neurogenic niches - is observed in the postnatal period. It is believed that astrocytes in the composition of neurogenic niches play a significant role in the regulation of neurogenesis, and therefore they are considered as a promising "target" for the possible control of neurogenesis, including the use of optogenetics. In the framework of this work, we formed an in vitro model of a neurogenic niche, consisting of cerebral endothelial cells, astrocytes and neurospheres. Astrocytes in the neurogenic niche model expressed canalorodopsin ChR2 and underwent photoactivation. The effect of photoactivated astrocytes on the expression profile of neurogenic niche cells was evaluated using immunocytochemical analysis methods. It was found that intact astrocytes in the composition of the neurogenic niche contribute to neuronal differentiation of stem cells, as well as the activation of astroglia expressing photosensitive proteins, changes the expression of molecules characterized by intercellular interactions of pools of resting and proliferating cells in the composition of the neurogenic niche with the participation of NAD+ (Cx43, CD38, CD157), lactate (MCT1). In particular, the registered changes reflect a violation of the paracrine intercellular interactions of two subpopulations of cells, one of which acts as a source of NAD+, and the second as a consumer of NAD+ to ensure the processes of intracellular signal transduction; a change in the mechanisms of lactate transport due to aberrant expression of the lactate transporter MCT1 in cells forming a pool of cells developing along the neuronal path of differentiation. In general, with photostimulation of niche astrocytes, the total proliferative activity increases mainly due to neural progenitor cells, but not neural stem cells. Thus, optogenetic activation of astrocytes can become a promising tool for controlling the activity of neurogenesis processes and the formation of a local proneurogenic microenvironment in an in vitro model of a neurogenic niche.

[Ligands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of Inflammation].

The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RA GE are well-known: advanced glycation end products (AGE), amyloid-beta (Aß), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 u S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.

Blebbing of thymocyte plasma membrane and apoptosis are related to impairment of capacitance Ca2+ entry into cells.

We studied the role of disturbances in cell Ca(2+) homeostasis in plasma membrane blebbing and death of thymocytes. Capacitance Ca(2+) channels of the plasma membrane and intracellular Ca(2+) stores are involved in the induction and progression of changes in the membrane and cytoskeleton and apoptosis induced by acrylonitrile.

Induction of apoptosis in bone marrow cells is mediated via purinergic receptors.

ATP activity in mouse bone marrow cells was in vitro estimated by expression of phosphatidylserine on the outer membrane surface using FITC-labeled annexin. ATP induced apoptosis in bone marrow cells. Purinergic receptor antagonists PPADS and suramin modulated the apoptotic effect of ATP on hemopoietic cells. Acute and subacute administration of doxorubicin, an inductor of oxidative burst, decreased cell sensitivity to ATP and abolished its apoptotic effect.

Doxorubicin modulates biological effects of ATP in bone marrow cells in vitro.

ATP activity in mouse bone marrow cells was studied in in vitro experiments. ATP in physiological and supraphysiological concentrations stimulated blebbing of the plasma membrane. Subacute administration of doxorubicin (inductor of oxidative stress) decreased cell sensitivity to ATP, which corresponded to changes in membrane lipid peroxidation.