Shishkina Tatiana V, Mishchenko Tatiana A, Mitroshina Elena V, Shirokova Olesya M, Pimashkin Alexei S, Kastalskiy Innokentiy A, Mukhina Irina V, Kazantsev Victor B, Vedunova Maria V
National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospect Gagarina, Nizhny Novgorod 603950, Russia.
National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospect Gagarina, Nizhny Novgorod 603950, Russia; Nizhny Novgorod State Medical Academy, 10/1 Minin and Pozharsky Square, Nizhny Novgorod 603950, Russia.
Brain Res. 2018 Jan 1;1678:310-321. doi: 10.1016/j.brainres.2017.10.023. Epub 2017 Nov 8.
Glial cell line-derived neurotrophic factor (GDNF) is regarded as a potent neuroprotector and a corrector of neural network activity in stress conditions. This work aimed to investigate the effect of GDNF on primary hippocampal cultures during acute normobaric hypoxia. 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.
胶质细胞系源性神经营养因子（GDNF）被视为一种强效的神经保护剂，也是应激条件下神经网络活动的校正因子。这项工作旨在研究GDNF对急性常压缺氧条件下原代海马培养物的影响。使用源自小鼠胚胎（E18）的体外培养14天的培养物进行缺氧诱导，在缺氧前10分钟向培养基中预防性添加GDNF（1 ng/ml）。在缺氧后阶段进行了自发生物电活动分析，包括确定内部神经网络结构、形态学研究和活力测试。该研究表明，GDNF在常氧条件下不影响自发网络活动，但可保护培养物免于细胞死亡，并在缺氧期间维持网络活动。GDNF创造了独特的条件，即使在细胞线粒体受损的情况下也能支持细胞的活力。GDNF通过影响突触可塑性部分抵消了缺氧的后果。活体mRNA检测发现GluR2 mRNA阳性细胞较少，而GDNF在缺氧后阶段保留了这些细胞的数量。AMPA受体GluR2亚基合成的激活是GDNF神经保护作用的一种可能机制。
