REMOTE ISCHEMIC PRE- AND POSTCONDITIONING ABOLISHED DELAYED HIF-1a EXPRESSION IN THE RAT HIPPOCAMPUS ALONGSIDE WITH THE CORRECTION OF EXPERIMENTAL POST-TRAUMATIC STRESS DISORDER

Abstract

Aims of the study. To examine effects of remote ischemic pre- and postconditioning which prevents development of the experimental post-traumatic s tress disorder (PTSD) in rats on the dynamics of expression of regulatory a-subunit of hypoxia-inducible factor (HIF-1a) in hippocampus. Materials and methods. Using immunohistochemistry method, the level of HIF-1a immunoreactivity has been quantitatively assessed in the hippocampus of animals exposed to stressors in the “traumatic stress-restress” paradigm, and by using the three-time remote limb ischemia which prevented the formation of anxiety pathology in this model. Results. Development of the PTSD-like pathology in rats was accompanied by considerable and persistent (up to 10 days after restress) up-regulation of HIF-1a immunoreactivity level in the CA1 field and dentate gyrus of hippocampus. Conditioning remote ischemia applied before traumatic stress (preconditioning) or following restress (postconditioning) did not affect early post-stress induction of HIF-1a (the first day) but abolished the delayed overexpression of this factor (5-10 days). Conclusions. The data obtained support our recent hypothesis on the pathogenic role of increased HIF-1 factor activity for the development of stress-related anxiety and depressive disorders within the delayed time-period. This also gives evidence to the fact that normalization of delayed violations of HIF-1a expression is obviously the key link of stress-protective effects of remote ischemic conditioning.

Keywords

HIF-1a / HIF-1a / post-traumatic stress disorder / PTSD / remote ischemic preconditioning and postconditioning / anxiolytic effect / stress-protective action

References

[1] Liberzon I., Krstov M., Young E.A. Stress restress: effects on ACTH and fast feedback // Psychoneuroendocrinology. 1997. Vol. 22 (6). P. 443-453.

[2] Рыбникова Е.А., Миронова В.И., Тюлькова Е.И., Самойлов М.О. Анксиолитический эффект умеренной гипобарической гипоксии у крыс в модели посттравматического стрессового расстройства // ЖВНД им. И.П. Павлова. 2008. Т. 58, № 4. С. 486-492. [Rybnikova E.A., Mironova V.I., Tiul'kova E.I., Samoĭlov M.O. The anxyolytic effect of mild hypobaric hypoxia in a model of post-traumatic stress disorder in rats // Zh Vyssh Nerv Deiat Im I.P. Pavlova. 2008. Vol. 58 (4). P. 486-492].

[3] Рыбникова Е.А., Воробьев М.Г., Самойлов М.О. Гипоксическое посткондиционирование корректирует нарушения поведения крыс в модели посттравматического стрессового расстройства // ЖВНД им. И.П. Павлова. 2012. Т. 62, № 3. С. 364-371. [Rybnikova E.A., Vorob'ev M.G., Samoĭlov M.O. Hypoxic postconditioning corrects behavioral abnormalities in a model of post-traumatic stress disorder in rats // Zh Vyssh Nerv Deiat Im I.P. Pavlova. 2012. Vol. 62, No 3. P. 364-371].

[4] Baranova K.A., Rybnikova E.A., Samoilov M.O. The Dynamics of HIF-1α Expression in the Rat Brain at Different Stages of Experimental Posttraumatic Stress Disorder and its Correction with Moderate Hypoxia // Neurochemical Journal. 2017. Vol. 11, Nо 2. P. 149-156.

[5] Baranova K.A., Mironova V.I., Rybnikova E.A., Samoilov M.O. Characteristics of the Transcription Factor HIF-1α Expression in the Rat Brain during the Development of a Depressive State and the Antidepressive Effects of Hypoxic Preconditioning // Neurochemical Journal. 2010. Vol. 4, No 1. P. 35-40.

[6] Ren C., Gao M., Dornbos D. 3rd, Ding Y., Zeng X., Luo Y., Ji X. Remote ischemic post-conditioning reduced brain damage in experimental ischemia/reperfusion injury // Neurol. Res. 2011. Vol. 33. P. 514-519.

[7] Joseph B., Pandit V., Zangbar B., Kulvatunyou N., Khalil M., Tang A., O'Keeffe T., Gries L., Vercruysse G., Friese R.S., Rhee P. Secondary brain injury in trauma patients: the effects of remote ischemic conditioning // J. Trauma Acute Care Surg. 2015. Vol. 78. P. 698-703.

[8] Li S., Hu X., Zhang M., Zhou F., Lin N., Xia Q., Zhou Y., Qi W., Zong Y., Yang H., Wang T. Remote ischemic post-conditioning improves neurological function by AQP4 down-regulation in astrocytes // Behav. Brain Res. 2015. Vol. 289. P. 1-8.

[9] Baranova K.A. Mild hypoxic and remote ischemic preconditioning in the prevention and correction of anxiety and depressive disorders in animal models // Official J. of the Internat. Stress and Behavior Society. 2016. Vol. 5. P. 17.

[10] Wang G.L., Jiang B.H., Rue E.A., Semenza G.L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension // Proc. Nat. Acad. Sci. USA. 1995. Vol. 92. P. 5510-5514.

[11] Bell E.L., Chandel N.S. Mitochondrial oxygen sensing: regulation of hypoxia-inducible factor by mitochondrial generated reactive oxygen species // Essays Biochem. 2007. Vol. 43. P. 17-27.

[12] Wagner A.E., Huck G., Stiehl D.P., Jelkmann W., Hellwig-Bürgel T. Dexamethasone impairs hypoxia-inducible factor-1 function // Biochem. Biophys. Res. Commun. 2008. Vol. 372, Nо 2. P. 336-340.

[13] Richard D.E., Berra E., Pouyssegur J. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells // J. Biol. Chem. 2000. Vol. 275. P. 26765-26771.

[14] Senba E., Ueyama T. Stress-induced expression of immediate early genes in the brain and peripheral organs of the rat // Neurosci. Res. 1997. Vol. 29 (3). P. 183-207.

[15] Baranova K.A., Rybnikova E.A., Samoilov M.O. Involvement of the Transcription Factor c-Fos in the Protective Effect of Hypoxic Preconditioning in a Model of Post-Traumatic Stress Disorder in Rats // Neurochemical Journal. 2011. Vol. 5, Nо 4. P. 257-262.

[16] Paschos N., Lykissas M.G., Beris A.E. The role of erythropoietin as an inhibitor of tissue ischemia // Int. J. Biol. Sci. 2008. Vol. 10, Nо 4 (3). P. 161-168.

[17] Leonard M.O., Godson C., Brady H.R., Taylor C.T. Potentiation of glucocorticoid activity in hypoxia through induction of the glucocorticoid receptor // J. Immunol. 2005. Vol. 174, Nо 4. P. 2250-2257.

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Baranova K.A., Rybnikova E.A.