title: TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor.
abstract: The neuroprotective and antihypoxic effects of brain-derived neurotrophic factor (BDNF) on dissociated hippocampal cultures in a hypoxia model were investigated. These experiments demonstrate that 10 minutes of normobaric hypoxia increased the number of dead cells in primary culture, whereas a preventive application of BDNF increased the number of viable cells. Spontaneous bioelectrical and calcium activity in neural networks was analyzed using multielectrode arrays and functional intravital calcium imaging. The results indicate that BDNF affects the functional parameters of neuronal networks in dissociated hippocampal cultures over the 7-day posthypoxic period. In addition, the effects of k252a, an antagonist of tropomyosin-related kinase B (TrkB), on functional bioelectrical activity during and after acute hypoxia were investigated. It was shown that the protective effects of BDNF are associated with binding to the TrkB receptor. Finally, intravital fluorescent mRNA probes were used to study the role of NF-κB1 in the protective effects of BDNF. Our experiments revealed that BDNF application stimulates NF-κB1 mRNA synthesis in primary dissociated hippocampal cells under normal conditions but not in hypoxic state.
authors.affiliation: Laboratory for Neuroprotection Methods Development, Nizhny Novgorod Neuroscience Centre, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia ; Molecular and Cell Technologies Group, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Vedunova
authors.affiliation: Laboratory for Neuroprotection Methods Development, Nizhny Novgorod Neuroscience Centre, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia ; Molecular and Cell Technologies Group, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Mishchenko
authors.affiliation: Laboratory for Neuroprotection Methods Development, Nizhny Novgorod Neuroscience Centre, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia ; Molecular and Cell Technologies Group, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Mitroshina
authors.affiliation: Laboratory for Neuroprotection Methods Development, Nizhny Novgorod Neuroscience Centre, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia ; Molecular and Cell Technologies Group, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Mukhina
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D016328:NF-kappa B; D012333:RNA, Messenger; C049985:staurosporine aglycone; D020813:Receptor, trkB