The effect of the GDNF factor on the activity of neural networks during hypoxic damage has been studied
Searching for ways to reduce losses from ischemic stroke, a major problem worldwide, is an extremely important task for many areas of public health and economy. So far, no effective and safe methods have been developed for treating ischemic brain damage.
One of the most promising approaches to the development of treatment methods is to use endogenous molecules (the molecules that are present in the body and perform the function of regulating various processes in the cells). Among such promising molecules are neurotrophic factors that regulate the development and survival of nerve cells, their "destiny", and can increase their resistance to adverse effects. One of the neurotrophic factors is the glial cell line-derived neurotrophic factor (GDNF).
The focus of the research of Lobachevsky University scientists was on how the GDNF affects the activity of neural networks during hypoxic damage. For many years, neurons were considered the main units of the nervous system. Today, neuroscience has come to the understanding that neural networks rather than separate cells should be regarded as the functioning units of the nervous system. It is the neural network that is the minimum link responsible for the processes of information processing, storage and reproduction. Therefore, to study the functional state of neural networks at the cellular and molecular level, primary cultures of hippocampal nerve cells were selected as the object of investigation.
Hypoxia induction was performed using day 14 in vitro cultures derived from mouse embryos (E18) with the preventive addition of GDNF (1 ng/ml) to the culture medium 10 min before oxygen deprivation. An analysis of spontaneous bioelectrical activity that included defining the internal neural network structure, morphological studies, and viability tests was performed during the post-hypoxic period. This study revealed that GDNF does not influence spontaneous network activity during normoxia but protects cultures from cell death and maintains the network activity during hypoxia. GDNF created unique conditions that supported the viability of cells even in cases of cellular mitochondrial damage. GDNF partially negated the consequences of hypoxia by influencing synaptic plasticity. Intravital mRNA detection identified fewer GluR2 mRNA-positive cells, whereas GDNF preserved the number of these cells in the post-hypoxic period. Activation of the synthesis of GluR2 subunits of AMPA-receptors is one possible mechanism of the neuroprotective action of GDNF.
The results obtained by the researchers provide a basis for developing new approaches to correcting the negative consequences of ischemic brain injury.