TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor.

Maria V Vedunova,Tatiana A Mishchenko,Elena V Mitroshina,Irina V Mukhina

doi:10.1155/2015/453901

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.

Highlights

Hypoxia is thought to be one of the main contributors to ischemic tissue damage
The pattern of spontaneous bioelectrical activity changed with respect to the number of small bursts, and we observed an insignificant increase in the average number of spikes per burst
The carried out experiments revealed acute hypoxia to cause irreversible changes in the functional bioelectrical and calcium network activity and reduces the viability of cells in dissociated hippocampal cultures

Summary

Introduction

Hypoxia is thought to be one of the main contributors to ischemic tissue damage. Changes in neuronal oxygen metabolism can alter many processes, including synaptic transmission and cell death, leading to the destruction of neural networks in the brain [1, 2]. Brain-derived neurotrophic factor (BDNF) is one factor that can control cellular metabolic rates under low oxygen conditions and promotes neuronal survival [3, 4]. This protein plays an important role in neuronal differentiation and the development of synaptic contacts during neurogenesis, but it can act as a modulator of mature neuronal metabolism [5,6,7,8,9,10]. Increased NF-κB1 mRNA synthesis induced by BDNF may be considered one of the possible mechanisms through cell metabolism alteration as a response to low oxygen conditions

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Discussion

Conclusion