Glial cell line-derived neurotrophic factor (GDNF) counteracts hypoxic damage to hippocampal neural network function &ITin vitro&IT

被引：17

作者：

Shishkina, Tatiana V. ^{[1
]}

Mishchenko, Tatiana A. ^{[1
,2
]}

Mitroshina, Elena V. ^{[1
,2
]}

Shirokova, Olesya M. ^{[2
]}

Pimashkin, Alexei S. ^{[1
]}

Kastalskiy, Innokentiy A. ^{[1
]}

Mukhina, Irina V. ^{[1
,2
]}

Kazantsev, Victor B. ^{[1
]}

Vedunova, Maria V. ^{[1
]}

机构：

[1] Natl Res Lobachevsky State Univ Nizhni Novgorod, 23 Prospect Gagarina, Nizhnii Novgorod 603950, Russia

[2] Nizhny Novgorod State Med Acad, 10-1 Minin & Pozharsky Sq, Nizhnii Novgorod 603950, Russia

来源：

BRAIN RESEARCH | 2018年 / 1678卷

基金：

俄罗斯科学基金会;

关键词：

Glial cell line-derived neurotrophic factor (GDNF); Primary hippocampal culture; Hypoxia; Neuroprotection; Multielectrode arrays; Intravital mRNA detection; INWARD RECTIFICATION; RECEPTOR; MECHANISMS; NEURONS; FAMILY; AMPA;

D O I：

10.1016/j.brainres.2017.10.023

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (C) 2017 The Author(s). Published by Elsevier B.V.

引用

页码：310 / 321

页数：12

共 24 条

[1] The GDNF family: Signalling, biological functions and therapeutic value [J].