CHANGES IN THE NEUROGENIC NICHE OF THE RAT HIPPOCAMPUS UNDER HYPOXIC EXPOSURE

Abstract

One of the most vulnerable brain structures to hypoxia is the hippocampus. Maintenance of the neurogenic niche cell pool in the subgranular zone of the hippocampus (SGZ) is provided by adaptive mechanisms. Among them are changes in the functional activity of mitochondrial respiratory chain complexes and the reaction of astroglia, which provides metabolic support for neurons. In order to study the dynamics of adaptive changes in neurons and glia in the dentate gyrus of the hippocampus under hypoxic conditions on a model of intermitten hypobaric hypoxia (5000 m, equivalent to 10.5% O2), with a single (60 min) and multiple (8 and 20 episodes) exposure in low-resistant rats, immunomorphological methods revealed the features of localization and content in the neurons of complex IV mitochondrial respiratory chain (MTCO1), astrocyte marker proteins glutamine synthetase (GS) and GFAP, and doublecortin (DCX) in immature neurons. With a single hypoxia, the content of MTCO1 in neurons significantly increased, and after eight exposures, the amount of glutamine synthetase (GS) in astrocytes of the dentate gyrus of the hippocampus increased. Changes in the content of GS were most pronounced in the processes of astrocytes, which indicates a redistribution of GS. The number of DCX+ neurons in the SGZ significantly decreased after 20 episodes of hypoxia. At the same time, DCX+ cells of glial morphology were found in the polymorphic layer, and staining for GFAP showed an increase in the number of astrocytes. This may be due to a shift in the direction of cell differentiation in the neurogenic niche. Thus, in hypoxia, at the initial stage, a functional restructuring of the respiratory chain of neurons of the granular layer occurs. Subsequently, it is noted by the activation of astrocytes that modulate glutamate metabolism. The presence of a relationship between the dynamics of adaptive reactions of energy exchange in neurons and glia and changes in neurogenesis during 20 episodes of hypoxia suggests that during long-term hypoxia, the differentiation of neural precursors of SGZ in the direction of astroglia occurs, however, this issue requires further study in order to more accurately determine the nature of DCX+ cells.