ABSTRACT
The expression of neurogenesis marker--NeuroD2 transcription factor--in the hippocampal dentate gyrus was studied in rats exposed to severe destructive hypoxia, a single or three episodes of moderate hypobaric hypoxia, preconditioned severe hypoxia, and severe hypoxia followed by 3 sessions of postconditioning by moderate hypobaric hypoxia. All the studied hypoxic exposure modes led to an increase of NeuroD2 level. Three-fold moderate hypoxia per se and in the preconditioning mode (followed by exposure to severe hypoxia) produced most pronounced up-regulatory effect on NeuroD2 expression. The results indicated that stimulation of neurogenesis processes seemed to be one of the aspects of the neuroprotective effect of three-fold preconditioning moderate hypoxia, but not of hypoxic postconditioning.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Hypoxia/physiology , Dentate Gyrus/metabolism , Ischemic Preconditioning , Neuropeptides/metabolism , Adaptation, Physiological/physiology , Animals , Male , Neurogenesis/physiology , Neuroprotective Agents , Rats , Rats, WistarABSTRACT
Using the method of quantitative immunohistochemistry, the expression of antiapoptotic protein Bcl-2 and neurotrophin BDNF was studied in CA1 hippocampal field of rats that survived severe hypoxia (SH), the damaging effects of which were compensated by subsequent three postconditioning (PC) sessions of mild hypobaric hypoxia (360 mm Hg, 2 hours, three times with 24 hour intervals). It was shown that the expression of the proteins studied was decreased in rat hippocampus after SH. Hypoxic postconditioning which improved the structural and functional rehabilitation after SH, was shown to up-regulate the expression of Bcl-2 and BDNF in hippocampal CA1 neurons in rats that survived SH. These results suggest the involvement of Bcl-2 and BDNF in processes of adaptation to SH and compensation of its damaging effects.
Subject(s)
Brain-Derived Neurotrophic Factor/biosynthesis , CA1 Region, Hippocampal/metabolism , Hypoxia, Brain/metabolism , Ischemic Preconditioning , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Animals , CA1 Region, Hippocampal/pathology , Hypoxia, Brain/pathology , Male , Rats , Rats, WistarABSTRACT
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.
