BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia,Promoting Survival of GABAergic Neurons

作     者：M.V.Turovskaya S.G.Gaidin M.V.Vedunova A.A.Babaev E.A.Turovsky M.V.Turovskaya;S.G.Gaidin;M.V.Vedunova;A.A.Babaev;E.A.Turovsky

作者机构：Institute of Cell Biophysics of the Russian Academy of SciencesFederal Research Center“Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”PushchinoRussia Institute of Biology and BiomedicineLobachevsky State University of Nizhny NovgorodNizhny NovgorodRussia 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2020年第36卷第7期

页      面：733-760页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 

基　　金：supported by grants from the President of Russian Federation(MK-677.2019.4 and MK626.2018.4) by RFBR according to the research project No. 20-04-00053 (vesicular release experiments) Virus construct was developed in the frameworks of the state project “Provision of scientific researches”(6.6379.2017/8.9) Development of ischemialike conditions model and cell viability tests was supported by a grant from the Russian Science Foundation(RSF)(18-75-10071) 

主　　题：Hypoxia Neuron BDNF Preconditioning Calcium Receptors 

摘      要：Hypoxia causes depression of synaptic plasticity,hyperexcitation of neuronal networks,and the death of specific populations of ***,brief episodes of hypoxia can promote the adaptation of *** preconditioning is well manifested in glutamatergic neurons,while this adaptive mechanism is virtually suppressed in GABAergic ***,we show that brain-derived neurotrophic factor(BDNF) overexpression in neurons enhances the preconditioning effect of brief episodes of *** amplitudes of the NMDAR-and AMPARmediated Ca2+ responses of glutamatergic and GABAergic neurons gradually decreased after repetitive brief hypoxia/reoxygenation cycles in cell cultures transduced with the(AAV)-Syn-BDNF-EGFP virus *** contrast,the amplitudes of the responses of GABAergic neurons increased in non-transduced cultures after *** decrease of the amplitudes in GABAergic neurons indicated the activation of mechanisms of hypoxic *** suppressed apoptotic or necrotic cell *** effect was most pronounced in cultures with BDNF overe *** of BDNF abolished the effect of preconditioning and promoted the death of GABAergic ***,the expression of the anti-apoptotic genes Stat3,Socs3,and Bcl-x1 substantially increased 24 h after hypoxic episodes in the transduced cultures compared to *** expression of genes encoding the pro-inflammatory cytokines IL-10 and IL-6 also *** turn,the expression of pro-apoptotic(Bax,Casp-3,and Fas) and proinflammatory(IL-1β and TNFα) genes decreased after hypoxic episodes in cultures with BDNF *** of vesicular BDNF release abolished its protective action targeting inhibition of the oxygen-glucose deprivation(OGD)-induced [Ca2+]i increase in GABAergic and glutamatergic neurons,thus promoting their *** A1,Brefeldin A,and tetanus toxin suppressed vesicular release(including BDNF) and shifted the gene expression pr