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

Abstract

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.

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