[Show abstract][Hide abstract] ABSTRACT: The study assessed involvement of Ca 2? sig-naling mediated by the metabotropic glutamate receptors mGluR1/5 in brain tolerance induced by hypoxic precon-ditioning. Acute slices of rat piriform cortex were tested 1 day after exposure of adult rats to mild hypobaric hypoxia for 2 h at a pressure of 480 hPa once a day for three consecutive days. We detected 44.1 ± 11.6 % suppression of in vitro anoxia-induced increases of intracel-lular Ca 2? levels and a fivefold increase in Ca 2? transients evoked by selective mGluR1/5 agonist, DHPG. Western blot analysis of cortical homogenates demonstrated a 11 ± 4 % decrease in mGluR1 immunoreactivity (IR), and in the nuclei-enriched fraction a 12 ± 3 % increase in IR of phospholipase Cb1 (PLCb1), which is a major mediator of mGluR1/5 signaling. Immunocytochemical analysis of the cortex revealed increase in the mGluR1/5 and PLCb1 IR in perikarya, and a decrease in IR of the neuronal inositol trisphosphate receptors (IP3Rs). We suggest that enhanced expression of mGluR5 and PLCb1 and potenti-ation of Ca 2? signaling may represent pro-survival upreg-ulation of Ca 2?-dependent genomic processes, while decrease in mGluR1 and IP3R IR may be attributed to a feedback mechanism preventing excessive intracellular Ca 2? release.
Neurochemical Research 08/2015; DOI:10.1007/s11064-015-1708-9 · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A quantitative immunohistochemical method was used to study the expression of antiapoptotic protein Bcl-2 and neurotrophin BDNF in hippocampal field CA1 in rats subjected to severe hypoxia (SH), the harmful consequences of which were compensated by three subsequent sessions of postconditioning (PostC) with moderate hypobaric hypoxia (360 mmHg, 2 h, three times with 24-h intervals). Decreases in the expression of these proteins were seen in the hippocampus of rats after SH. Hypoxic PostC, which improves structural-functional rehabilitation after severe hypoxia, increased Bcl-2 and BDNF expression in neurons in hippocampal field CA1 in rats subjected to SH. The results provided evidence of the involvement of Bcl-2 and BDNF in the processes of adaptation to SH and compensation of its damaging effects.
Neuroscience and Behavioral Physiology 05/2015; 45(4):367-370. DOI:10.1007/s11055-015-0083-y
[Show abstract][Hide abstract] ABSTRACT: 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. The effect of preconditioning with one trial of MHH (360 mmHg) on Bcl-2 expression was similar to that seen after SH. In contrast, preconditioning with repeated exposures to MHH significantly up-regulated Bcl-2 expression levels 3-24 h after SH that apparently protected neurons from SH-induced injury. MHH alone, not followed by SH, significantly increased Bcl-2 expression only after multiple (three or six) exposures whereas single MHH exposure had no effect on Bcl content. Hence, up-regulation of Bcl-2 seen in response to multiple MHH trials appears to be important for the formation of the mechanisms of brain neuronal tolerance to damaging factors.
[Show abstract][Hide abstract] ABSTRACT: Hippocampal gluco- and mineralocorticoid receptors (GR, MR) have important roles in the mechanisms regulating the activity of the hypothalamo-hypophyseal-adrenocortical system (HHAS), neuron survival/death, learning, and memory. Imbalance in MR and GR contents lead to impairments of HHAS activity and can promote neuron damage/death in extreme conditions. The present study used a quantitative immunocytochemistry method to provide the first comparative analysis of the effects of different regimes of hypobaric hypoxia on the nature of GR and MR expression in the dorsal (CA1) and ventral (dentate gyrus) parts of the hippocampus in rats. The data obtained here showed that severely harmful hypoxia induces marked impairments to the expression of both GR and MR in CA1 and dental gyrus cells, which correlated with damage/death of a significant proportion of neurons in CA1 and dysregulation of the activity of the HHAS. Series of three and six sessions (but not one session) of preconditioning with moderate hypoxia preceding severe hypoxia prevented these impairments.
Neuroscience and Behavioral Physiology 07/2014; 44(6):717-724. DOI:10.1007/s11055-014-9974-6
[Show abstract][Hide abstract] ABSTRACT: Using immunohistochemistry, we studied the expression of the alpha regulatory subunit of the hypoxia-inducible factor (HIF-1α) and the product of its target gene, which encodes the protective cytokine erythropoietin in the hippocampal CA1 field of rats in response to damaging severe hypoxia and severe hypoxia followed by three sessions of postconditioning with mild hypobaric hypoxia. We found that the immunoreactivity to the proteins studied in the hippocampus of rats was reduced in response to severe hypoxia. Hypoxic postconditioning sessions of mild hypobaric hypoxia (360 mmHg, 2 h, three times at intervals of 24 h) up regulated the expression of HIF-1α and erythropoietin in hippocampal CA1 neurons of rats that survived after severe hypoxia. Our results indicate that postconditioning led to compensation of hypoxia-induced neuron damage in the brain, which actively involved HIF-1α and erythropoietin.
[Show abstract][Hide abstract] ABSTRACT: A comparative analysis of the effects of severe hypobaric hypoxia in different prenatal periods on expression profiles of glucocorticoid receptors (GR) in dorsal (CA1) and ventral (dental gyrus) hippocampus and neocortex of rats, their stress reactivity and working memory has been performed in the present study for the first time. According to the data obtained, severe hypoxia in the prenatal period induces remarkable disturbances of GR expression in the neurons of neocortex of adult males but not females, that correlates to the disruption of working memory in adult males exposed to hypoxia on the prenatal 14-16th days. Elevation of stress plasma corticosterone levels have been observed only in the females subjected to hypoxia on the prenatal 17-19th days. Hypoxia in the females and males results in the differential changes in functions of hippocampus, as well as of other brain areas involved in learning.
[Show abstract][Hide abstract] ABSTRACT: 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. Multiple (but not single one) trials of preconditioning using mild HH which reduce neuronal damage promote p65 expression and prevent suppression of c-Rel level after SH. Triple session of mild HH itself when applied as a preconditioning stimulus upregulate expression of both subunits, while single administration or sixfold trials has no effect on the level of immunoreactivity of both subunits. The revealed peculiarities of the expression of p65 and c-Rcl implies that these subunits of NF-kappaB appear to contribute to the mechanisms of brain tolerance to SH.
[Show abstract][Hide abstract] ABSTRACT: Using quantitative immunohistochemistry, neuronal expression of alpha-subunit of the transcriptional factor HIF-1 in hippocampus and neocortex of rats in response to pathogenic psychoemotional (model of posttraumatic stress disorder, PTSD) and hypoxic (severe hypobaric hypoxia, 180 Torr, 3 h), as well as to neuroprotective exposures to hypoxic pre- and postconditioning has been studied. Elongated overexpression of HIF-1alpha in hippocampus and neocortex of rats in response to the psychoemotional stress in PTSD paradigm, but not hypoxic stress, has been observed. Hypoxic pre- and postconditioning with mild hypobaric hypoxia (360 Torr, 2 h, 3 trials spaced at 24 h), those induced adaptation to the psychoemotional stress, abolished the elongated HIF-1alpha overexpression. Hypoxic postconditioning which improved structure and functional rehabilitation following severe hypoxic stress up-regulated HIF-1alpha expression in the brain neurons of rats survived severe hypoxia. The findings indicate that transcription factor HIF-1 is particularly involved in the processes of adaptation/ maladaptation to the action of injurious stresses, but its role depends upon the nature of stressor.
[Show abstract][Hide abstract] ABSTRACT: The effects of repetitive mild hypobaric hypoxic preconditioning upon pro- and antioxidant systems in rat hippocampus were studied. It was found that three-trial preconditioning by mild hypobaric hypoxia (360 mm Hg, 2 h) induced moderate oxidative stress immediately after the last preconditioning trial. In addition, it down-regualted the levels of peptide antioxidants (Trx-1, Trx-2, Cu,Zn-SOD) and several lipid peroxidation products 24 h later.
[Show abstract][Hide abstract] ABSTRACT: 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. According to the data obtained, severe injurious hypoxia induced prominent disturbances of GR and MR expression in the cells of CA1 and dentate gyrus that correlated to the remarkable neuronal injury/loss in CA1 and dysregulated HPA activity. Sets of three- or six-trial (but not one-trial) preconditioning using mild hypoxia prior to severe hypoxia prevented these abnormalities.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 02/2013; 98(11):1380-95.
[Show abstract][Hide abstract] ABSTRACT: Group I of metabotropic glutamate receptors (ImGluRs) are a family of G-protein-coupled receptors which activate a multitude of signaling pathways important for modulating neuronal excitability and synaptic plasticity as well as anti- and prosurvival pathways initiated by hypoxia. However these functions are still not complete and sometimes controversial. The present work is a review of data concerning involvement of ImGluRs in mechanisms of cell response to hypoxia. We also present original data demonstrating their participation in forming pathogenic and adaptogenic intracellular events, appearing in rat neocortex during a day after severe or moderate hypobaric hypoxia, respectively. Ca2+ responses to ImGluRs stimulation in survival cortical slices and expression of ImGluRs, IP3Rs and PLCbeta1 in immunolabelled cortical preparations were estimated for these two different hypoxic models.
Patologicheskaia fiziologiia i eksperimental'naia terapiia 10/2012;
[Show abstract][Hide abstract] ABSTRACT: 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. The preconditioning using mild hypobaric hypoxia (pressure equal to 360 Torr) had varied effect on the morphological characteristics of brain neurons of rats, subjected to severe hypoxia. Multiple (three-trial or six-trial) preconditioning prevents structural damage of neurons induced by subsequent severe hypoxia. On the contrary, single preconditioning trial of mild hypoxia was ineffective in terms of neuroprotection.
[Show abstract][Hide abstract] ABSTRACT: 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. The study addressed changes in the expression of transcription factors NF-kappaB (nuclear factor kappa B) and CREB (cAMP response element binding protein) in the hippocampus of rats preconditioned with moderate hypoxia. Immunocytochemical methods demonstrated that HP increased immunoreactivity for NF-kappaB and phosphorylated CREB (pCREB) in hippocampal fields CA1-CA4 and the dentate gyrus and promoted increases in the expression of these transcription factors in the hippocampus of preconditioned rats 3-24 h after severe hypobaric hypoxia. These data provide evidence that NF-kappaB and CREB are involved in the mechanisms forming HP-induced tolerance of the brain.
Neuroscience and Behavioral Physiology 10/2010; 40(8):852-7. DOI:10.1007/s11055-010-9340-2
[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated that preconditioning (PC) with three sessions of moderate hypoxia significantly increases the expression of the antioxidant protein thioredoxin-1 (Trx-1) in the rat hippocampus by 3 h after subsequent acute severe hypoxia as compared with non-preconditioned animals. However, it remained unclear whether this increase in Trx-1 accumulation during PC is induced before severe hypoxia or is a modification of the response to severe hypoxia. This question was addressed in the present investigation using experiments on 12 adult male Wistar rats with studies of Trx-1 expression after PC without subsequent severe hypoxia. Immunocytochemical studies were performed 3 and 24 h after three episodes of moderate hypobaric hypoxia (three sessions of 2 h at 360 mmHg with 24-h intervals). Immunoreactivity to Trx-1 24 h after the last session was significantly decreased in neurons in all the areas of the hippocampus studied (CA1, CA2, CA3, and the dentate gyrus). Immunoreactivity in CA3 was also decreased 3 h after hypoxia. These results provide evidence that moderate preconditioning hypoxia itself not only does not increase, but even significantly decreases Trx-1 expression. Thus, increases in Trx-1 contents in the hippocampus of preconditioned animals after severe hypoxia are not associated with the accumulation of this protein during PC, but with a PC-induced modification of the reaction to severe hypoxia.
Neuroscience and Behavioral Physiology 01/2009; 39(1):1-5. DOI:10.1007/s11055-008-9091-5
[Show abstract][Hide abstract] ABSTRACT: The effect of preconditioning by a moderate hypobaric hypoxia on changes in the activity of the mitogen-activated (MAP) kinases
EPK, JNK 1/2, and p38 and the c-Jun transcriptional factor in rat hippocampus in response to the severe hypoxia was studied
using the methods of quantitative immunocytochemistry and Western-blot analysis. Severe damaging hypoxia caused a persistent
activation of the JNK cascade, including JNK 1/2 and c-Jun, and also p38 kinase in the hippocampus cells. The preconditioning
efficiently inhibited the expression of phosphorylated forms of JNK, c-Jun, and p38 and activated the protein kinase ERK following
the severe hypoxia, which obviously promoted the survival of hippocampal neurons. The results indicate the important role
of the family of MAP kinases and the c-Jun transcription factor in the processes of neuronal death/survival of the hippocampal
neurons after a severe hypobaric hypoxia, and a correcting effect of preconditioning action.
[Show abstract][Hide abstract] ABSTRACT: The Nissl method and immunocytochemistry were used to study the effects of severe hypobaric hypoxia and its actions in combination with the preconditioning actions of moderate hypoxia on the expression of the early gene proteins c-Fos and NGFI-A as well as structural changes in hippocampal and neocortical neurons in the rat brain. Severe hypoxia was found to suppress c-Fos and NGFI-A synthesis (3-24 h after exposure) and to induce delayed (days 3-7) structural damage to neurons, of the "light" and predominantly the "dark" types, which appear to reflect the development of necrotic and apoptotic processes respectively. Preconditioning with the regime used here corrected these derangements, resulting in increases in the expression of early gene proteins and significant reductions in structural damage to neurons after severe hypoxia.
Neuroscience and Behavioral Physiology 06/2005; 35(4):383-8. DOI:10.1007/s11055-005-0037-x
[Show abstract][Hide abstract] ABSTRACT: The effects of severe hypobaric hypoxia and preconditioned severe hypoxia on the expression of early genes products--proteins c-Fos and NGFI-A, and structural changes in rat hippocampal and neocortical neurons were studied using Nissl staining and immunocytochemistry. Severe hypoxia was found to induce a suppression of c-Fos and NGFI-A synthesis (at 3-24 h after exposure) and delayed (by day 3-7) destructive neuronal changes, which developed according to "light" and predominantly "dark" type, that obviously reflected necrotic or apoptotic processes, respectively. The preconditioning in the regime applied abolished these pathological changes, as expressed by stimulation of early gene products expression and marked reduction of neuronal damage following severe hypoxia.
[Show abstract][Hide abstract] ABSTRACT: Levels of the acidic brain-specific Rf = 0.58 protein in neurons of the subglottal complex of ganglia were studied in the common snail during the process of acquisition of defensive food aversion. Levels were significantly increased in neurons LPa3 and RPa3 at both the early and late stages of learning. There was a tendency to increased protein levels in neurons LP11 and RP12, while there were no changes in levels in neuron RPa5 and pool D. The level of involvement of defensive behavior command neurons appears to be determined by the specific involvement of their receptor and effector fields.
Neuroscience and Behavioral Physiology 02/2003; 33(1):49-52. DOI:10.1023/A:1021127314745
[Show abstract][Hide abstract] ABSTRACT: At early stages of aversive conditioning in Helix, a most considerable increase in the acid brain-specific protein Rf 0.58 occurred in LPa3 and PPa3 neurones. Later the content of this protein decreased in the PPa3 but went on increasing in LPa3. In sham learning, the protein content did not increase so obviously. Hence the protein Rf 0.58 metabolism in individual neurones of the snail CNS correlates with the draw step of receptor and effector fields in avoidance conditioning.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 07/2001; 87(6):774-8.
[Show abstract][Hide abstract] ABSTRACT: A 2-week neurotization of two rat lines formed a long-term stress and increased neuronal Na+,K(+)-ATPase activity in hippocampus, locus coeruleus and n. raphe dorsalis, whereas the glial enzyme activity was decreased in hippocampus and N. raphe dorsalis. (Line H). In rats with low threshold of excitability (line L), the decrease of the Na+,K(+)-ATPase activity occurred in n. raphe dorsalis and hippocampus. After a 15-day rest, the activity decreased in all the structures of the line rats, whereas in the line L rats the activity was still increased in hippocampal neurons. Differences between the rat lines and dependence of the enzyme activity on the functional state of the nervous system, are discussed.
Fiziologicheskiĭ zhurnal SSSR imeni I. M. Sechenova 03/1992; 78(2):1-7.