Differences in the Autophagy Response to Hypoxia in the Hippocampus and Neocortex of Rats.

Autophagy is a regulated mechanism of degradation of misfolded proteins and organelles in the cell. Neurons are highly differentiated cells with extended projections, and therefore, their functioning largely depends on the mechanisms of autophagy. For the first time in an animal model using immunohistochemistry, dot analysis, and qRT-PCR, the autophagy (macroautophagy) activity in neurons of two brain regions (hippocampus and neocortex) under normoxia and after exposure to hypoxia was studied.

Effects of Different Modes of Hypobaric Hypoxia on the Content of Epigenetic Factors in the Rat in Neurons of Rat Neocortex.

We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels.

Acetylation of histones in neocortex and hippocampus of rats exposed to different modes of hypobaric hypoxia: Implications for brain hypoxic injury and tolerance.

Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain.

[MORPHOLOGICAL DIFFERENCES BETWEEN THE EFFECTS OF VARIOUS MODES OF PRECONDITIONING AIMED AT CORRECTING THE DAMAGE TO THE HIPPOCAMPAL NEURONS BY SEVERE HYPOBARIC HYPOXIA].

In 5 groups of rats (6 animals in each), the changes of neurons in hippocampal fields CA1 and CA4 were studied 7 days after severe hypobaric hypoxia (180 mm Hg, for 3 h) preceded by various numbers (1, 3 and 6) of sessions of preconditioning (PC) by mild hypobaric hypoxia (360 mm Hg, for 2 h, 24 h prior to severe hypoxia). It was found that a single session of PC did not prevent the damage to the structure of neurons and their death after exposure to severe hypoxia. Meanwhile, 6, and especially 3 sessions of PC induced protective mechanisms of neuronal damage prevention.

Neocortical pCREB and BDNF expression under different modes of hypobaric hypoxia: role in brain hypoxic tolerance in rats.

Preconditioning with repetitive mild hypobaric hypoxia is known to increase tolerance of susceptible brain neurons to severe hypoxia, whereas a single trial of mild hypoxia has been ineffective. In the present study, the effects of three-trial and one-trial hypobaric preconditioning on the expression of the protective transcription factor phosphorylated CREB (pCREB) and neurotrophin BDNF, before and after severe hypobaric hypoxia, have been comparatively studied in the neocortex of rats. As revealed by quantitative immunocytochemistry, the severe hypobaric hypoxia (180 Torr, 3h) substantially down-regulated the levels of pCREB and BDNF in cortical neurons assessed 24h after the treatment.

[Changes in the expression of Bcl-2 antiapoptotic protein in rat neocortex and hippocampus under the influence of various modes of hypobaric hypoxia].

Using immunocytochemical method, the level of expression of Bcl-2 antiapoptotic factor was studied in neurons of the neocortex and hippocampus in 72 male Wistar rats exposed to damaging severe hypoxia (SH), moderate hypobaric hypoxia (MHH), as well as their combination. After SH (180 mmHg) Bcl-2 expression in the neurons of the brain regions examined was reduced or. unchanged.

[Effects of several modes of hypobaric hypoxia on expression profiles of corticosteroid receptors in rat hippocampus].

Gluco- and mineralocorticoid receptors are believed to play important roles in mechanisms of the hypothalamic-pituitary-adrenal axis (HPA) regulation, neuronal death/survival, as well as learning and memory processes. Imbalanced levels of MR and GR result in impairment of HPA activity and can promote neuronal injury and loss following exposures to extreme factors. In the present study, using quantitative immunohistochemistry, the comparative analysis of the effects of hypobaric hypoxia in several modes on expression profiles of GR and MR in dorsal (CA1) and ventral (dentate gyrus) hippocampus was performed.

[Pattern of neuronal expression of transcription factors NF-kappaB under different modes of hypobaric hypoxia].

Transcription factor NF-kappaB plays a pivotal role in mechanisms of brain neuron survival and degeneration under injurious stimuli, first of all different types of hypoxia. In the present work, using quantitative immunohystochemistry, we provide analysis of expression of different subunits of NF-kappaB (p65 and c-Rel) in the rat neocortex in response to severe injurious hypobaric hypoxia (HH) or after a single or multiple sessions of mild protective HH. Severe hypoxia (SH), resulting in loss of brain neurons, has no effect on the level of expression of p65 but suppresses expression of c-Rel.

[The effect of mild hypobaric hypoxia regime on expression of factor induced by hypoxia in the rat neocortex].

Using quantitative immunohistochemistry, modifications of HIF-1alpha expression in neocortex of rats exposed to various modes of mild hypobaric hypoxia (MHH) (1,3 and 6 episodes) differed in their neuroprotective efficacy have been studied. It has been shown that three-trial MHH being the most effective neuroprotective mode when used as a preconditioning produces most considerable changes in HIF-1 by substantial up-regulation of its regulatory alpha-subunit expression in the rat neocortex. Present findings support the hypothesis on important roles of HIF-1 in the mechanisms of brain hypoxic tolerance induced by the hypoxic preconditioning with three-trial MHH.

[Signal molecular and hormonal mechanisms of formation of the hypoxic preconditioning protective effects].

In the review, results of the long-standing authors'studies and literature data concerning one of the underresearched aspects of actual problem of induced brain tolerance to injurious factors - "preventive" signal function of the hypoxic preconditioning, as well as molecular and hormonal mechanisms underlying its protective effects are presented. Hypoxic preconditioning by using of mild hypobaric hypoxia in special mode mobilizes evolutionary acquired genome determined defense mechanisms of brain neurons and whole organism. This process involves an activation of multiple intracellular components, as well as hypothalamic-pituitary-adrenal axis.

[Changes in hippocampal and neocortical rat neurons induced by different regimes of hypobaric hypoxia].

Hypobaric hypoxia may have either detrimental or adaptive effect on structural and functional characteristics of brain neurons. In this study, the effect of different regimes of hypobaric hypoxia on the structural and functional characteristics of hippocampal and neocortical neurons was examined in rats (n = 30). It was shown that severe hypoxia (induced by pressure in the pressure chamber equal to 180 Torr) caused structural neuronal damage both in the fronto-parietal neocortex and dorsal and ventral hippocampus 3 days after the exposure.

Expression of glucocorticoid and mineralocorticoid receptors in hippocampus of rats exposed to various modes of hypobaric hypoxia: Putative role in hypoxic preconditioning.

Effects of mild (preconditioning) and severe injurious hypobaric hypoxia (SH), as well as of their combination on hippocampal expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and HPA axis activity have been examined in rats. As revealed by quantitative immunocytochemistry, three-trial exposure to mild hypoxia produced robust GR and MR overexpression located mainly in the neuronal nuclei in the dentate gyrus (DG) but only MR overexpression was observed in the CA1. SH induced sharp reduction of MR levels and enhanced GR expression in the CA1, suggesting that the unbalance of GR and MR observed might be at the bottom of the extensive neuronal loss seen in this area in response to SH.

Effects of moderate hypobaric hypoxic preconditioning on the expression of the transcription factors pCREB and NF-kappaB in the rat hippocampus before and after severe hypoxia.

Preconditioning using three sessions of moderate hypobaric hypoxia, i.e., hypoxic preconditioning (HP), increased the tolerance of susceptible brain neurons to severe hypoxia and other harmful factors.

[Effect of mild hypobaric hypoxia in the preconditioning regime on expression of pCREB and NF-kappaB transcription factors in the rat hippocampus before and after severe hypoxia].

Preconditioning using threefold mild hypobaric hypoxia (HH) is known to increase the tolerance of vulnerable brain neurons to severe hypoxia and other damaging factors. In the present study, the changes of the expression of transcription factors NF-kappaB (nuclear factor kappa B) and CREB (cAMP response element binding protein) were studied in the hippocampus of rats preconditioned by mild hypoxia. Using immunocytochemical method, it was demonstrated that HH increased NF-kappaB and phosphorylated CREB (pCREB) immunoreactivity in CA1-CA4 fields of the hippocampus and gyrus dentatus.

Preconditioning induces prolonged expression of transcription factors pCREB and NF-kappa B in the neocortex of rats before and following severe hypobaric hypoxia.

Preconditioning using mild repetitive hypobaric hypoxia is known to increase a tolerance of brain neurons to severe hypoxia and other injurious exposures. In the present study, the effects of mild hypoxic preconditioning on the expression of transcription factors NF-kappaB and phosphorylated CREB (pCREB) has been studied in the neocortex of rats exposed to severe hypobaric hypoxia. As revealed by quantitative immunocytochemistry, the injurious severe hypobaric hypoxia (180 Torr, 3 h) remarkably reduced the neocortical levels of pCREB and NF-kappaB.