BDNF-Mediated Regulation of the Brain Mitochondria Functional State in Hypoxia

Astrakhanova Т.А., Urazov М.D., Usenko А.V., Mitroshina Е.V., Mishchenko Т.А., Schelchkova N.А., Vedunova М.V.

Key words: brain-derived neurotrophic factor; BDNF; TrkB-signaling; acute hypobaric hypoxia; oxidative phosphorylation; neuroprotection.

2018, volume 10, issue 3, page 88.

DOI: https://doi.org/10.17691/stm2018.10.3.10

Full text

html pdf

2922

2807

Abstract
References
How to cite

The aim of the study was to study the effect of TrkB-mediated action of the brain-derived neurotrophic factor (BDNF) on animal survival and mitochondrial respiratory chain activity in acute hypobaric hypoxia model in vivo.

Materials and Methods. In vivo experiments were performed on mature male CBA mice weighing 20–25 g. In order to modulate acute hypobaric hypoxia, the animals were placed in the hypobaric chamber (220–240 mm Hg) which simulates conditions corresponding to the altitude of 10 000 m above sea level. The oxygen consumption rate by the brain mitochondria under the hypoxic influence was evaluated using a high-resolution OROBOROS Oxygraph-2k respirometer (OROBOROS Instruments, Austria).

Results. Preventive BDNF application has been established to increase the survival of the CBA-line animals after acute hypobaric hypoxia modeling and to influence favorably the work of mitochondrial respiratory chain complex I.

Conclusion. BDNF increases animal resistance to acute hypobaric hypoxia and influences the work of mitochondrial respiratory chain through TrkB-signaling mechanisms. Antihypoxic effect of BDNF is realized by maintaining the activity of NADH-dependent pathway of substrate oxidation and ATP synthesis.

Lukyanova L.D., Kirova Yu.I., Sukoyan G.V. Signaling mechanisms of adaptation to hypoxia and its role in systemic regulation. Biologicheskie membrany 2012; 29(4): 238–252.
Duchen M. Mitochondria in health and disease: perspectives on a new mitochondrial biology. Mol Aspects Med 2004; 25(4): 365–451, https://doi.org/10.1016/j.mam.2004.03.001.
Wheaton W.W., Chandel N.S. Hypoxia. 2. Hypoxia regulates cellular metabolism. Am J Physiol Cell Physiol 2011; 300(3): 385–393, https://doi.org/10.1152/ajpcell.00485.2010.
Hernansanz-Agustín P., Ramos E., Navarro E., Parada E., Sánchez-López N., Peláez-Aguado L., Cabrera-García J.D., Tello D., Buendia I., Marina A., Egea J., López M.G., Bogdanova A., Martínez-Ruiz A. Mitochondrial complex I deactivation is related to superoxide production in acute hypoxia. Redox Biol 2017; 12: 1040–1051, https://doi.org/10.1016/j.redox.2017.04.025.
Görlach A., Dimova E.Y., Petry A., Martínez-Ruiz A., Hernansanz-Agustín P., Rolo A.P., Palmeira C.M., Kietzmann T. Reactive oxygen species, nutrition, hypoxia and diseases: рroblems solved? Redox Biol 2015; 6: 372–385, https://doi.org/10.1016/j.redox.2015.08.016.
Olmez I., Ozyurt H. Reactive oxygen species and ischemic cerebrovascular disease. Neurochem Int 2012; 60(2): 208–212, from: https://doi.org/10.1016/j.neuint.2011.11.009.
Chaturvedi R.K., Flint Beal M. Mitochondrial diseases of the brain. Free Radic Biol Med 2013; 63: 1–29, https://doi.org/10.1016/j.freeradbiomed.2013.03.018.
Galkin A., Abramov A.Y., Frakich N., Duchen M.R., Moncada S. Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury? J Biol Chem 2009; 284(52): 36055–36061, https://doi.org/10.1074/jbc.m109.054346.
Markham A., Cameron I., Franklin P., Spedding M. BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II. Eur J Neurosci 2004; 20(5): 1189–1196, https://doi.org/10.1111/j.1460-9568.2004.03578.x.
Vedunova М.V., Sakharnova Т.А., Mitroshina E.V., Shishkina T.V., Astrakhanova T.A., Mukhina I.V. Antihypoxic and neuroprotective properties of BDNF and GDNF in vitro and in vivo under hypoxic conditions. Sovremennye tehnologii v medicine 2014; 6(4): 38–47.
Stragier E., Massart R., Salery M., Hamon M., Geny D., Martin V., Boulle F., Lanfumey L. Ethanol-induced epigenetic regulations at the Bdnf gene in C57BL/6J mice. Mol Psychiatry 2015; 20(3): 405–412, https://doi.org/10.1038/mp.2014.38.
Metodicheskie rekomendatsii po eksperimental’nomu izucheniyu preparatov, predlagaemykh dlya klinicheskogo izucheniya v kachestve antigipoksicheskikh sredstv [Guidelines on experimental study of drugs offered for clinical study as antihypoxic agents]. Pod red. Lukyanovoy L.D. [Lukyanova L.D. (editor)]. Moscow; 1990.
Egorova M.V., Afanasyev S.A. Isolation of mitochondria from cells and tissues of animals and human: modern methodical approaches. Sibirskij medicinskij zurnal 2011; 26(1–1): 22–28.
Vedunova M.V., Mishchenko T.A., Mitroshina E.V., Mukhina I.V. TrkB-mediated neuroprotective and antihypoxic properties of brain-derived neurotrophic factor. Oxid Med Cell Longev 2015; 2015: 453901, https://doi.org/10.1155/2015/453901.
Skaper S.D. Neurotrophic factors: an overview. Methods Mol Biol 2018; 1727: 1–17, https://doi.org/10.1007/978-1-4939-7571-6_1.
Kristián T. Metabolic stages, mitochondria and calcium in hypoxic/ischemic brain damage. Cell Calcium 2004; 36(3–4): 221–233, https://doi.org/10.1016/j.ceca.2004.02.016.
Lukyanova L.D. Signal role of mitochondria in adaptation to hypoxia. Fіzіologіchniy zhurnal 2013; 59(6): 141–154.

Astrakhanova Т.А., Urazov М.D., Usenko А.V., Mitroshina Е.V., Mishchenko Т.А., Schelchkova N.А., Vedunova М.V. BDNF-Mediated Regulation of the Brain Mitochondria Functional State in Hypoxia. Sovremennye tehnologii v medicine 2018; 10(3): 88, https://doi.org/10.17691/stm2018.10.3.10