Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

Abstract

Currently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain’s resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo. To achieve overexpression of neurotrophic factors in the central nervous system’s cells, viral constructs were injected into the brain ventricles of newborn male C57Bl6 (P0) mice. Acute hypobaric hypoxia was modeled on the 30th day after the injection of viral vectors. Survival, cognitive, and mnestic functions in the late post-hypoxic period were tested. Evaluation of growth and weight characteristics and the neurological status of animals showed that the overexpression of neurotrophic factors does not affect the development of mice. It was found that the use of adeno-associated viral vectors increased the survival rate of male mice under hypoxic conditions. The present study indicates that the neurotrophic factors’ overexpression, induced by the specially developed viral constructs carrying the BDNF and GDNF genes, is a prospective neuroprotection method, increasing the survival rate of animals after hypoxic injury.

Hypoxic Preconditioning Modulates BDNF and Its Signaling through DNA Methylation to Promote Learning and Memory in Mice

“…Furthermore, BDNF may also resist brain damage derived from hypoxia/ischemia . For example, upregulation of BDNF via the specially developed viral constructs may increase survival after hypoxic injury in animals . However, the effects of BDNF, TrkB receptor, and BDNF/TrkB signaling in neuroprotection of the HPC remain unclear.…”

“…8 This article is licensed under CC-BY-NC-ND 4 For example, upregulation of BDNF via the specially developed viral constructs may increase survival after hypoxic injury in animals. 9 However, the effects of BDNF, TrkB receptor, and BDNF/TrkB signaling in neuroprotection of the HPC remain unclear. Notably, BDNF can modulate synaptic plasticity, which is a molecular mechanism of learning and memory in development and adulthood via activation of BDNF/TrkB signaling.…”