Short-term hypoxia induces a selective death of GABAergic neurons

被引：10

作者：

Turovskaya M.V. ^{[1
]}

Turovsky E.A. ^{[1
]}

Kononov A.V. ^{[1
]}

Zinchenko V.P. ^{[1
]}

机构：

[1] Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Oblast, 142290, ul. Institutskaya

来源：

Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology | 2014年 / 8卷 / 1期

关键词：

GABAergic neurons; hyperexcitability; hypoxia; NMDA receptors; selective death;

D O I：

10.1134/S199074781305019X

中图分类号：

学科分类号：

摘要：

It is known that brief episodes of hypoxia protect neurons from death caused by global ischemia and hypoxia (hypoxic preconditioning). At the same time, brief hypoxia may cause a phenomenon of posthypoxic hyperexcitability during reoxygenation, which can lead to the death of separate neurons due to their individual differences. In this work we compare the effects of short-term hypoxia on the initiation of preconditioning and posthypoxic hyperexcitability in two populations of neurons: inhibitory GABAergic neurons and excitatory glutamatergic neurons. Preconditioning effect was evaluated according to the suppression of the NMDA-receptor activity. The phenomenon of posthypoxic hyperexcitability was estimated by the appearance of spontaneous synchronized Ca2+ spikes in the neuronal network during reoxygenation after each episode of hypoxia. It is shown that the preconditioning effect occurs only in glutamatergic neurons. In the GABAergic neurons the effect of preconditioning was not observed. The activity of NMDA receptors in these neurons was not suppressed but increased after each episode of hypoxia. At the moment of posthypoxic synchronous Ca2+-spike generation, a global increase of the cytoplasmic Ca2+ concentration occurred in a few of GABAergic neurons, followed by the apoptotic death of these cells. The anti-inflammatory cytokine, interleukin-10 (IL-10) prevented the development of posthypoxic hyperexcitability, inhibiting spontaneous synchronous Ca2+ spike, and protected GABAergic neurons from the death, restoring the preconditioning effect in them. PI3-kinase inhibitors wortmannin and LY294002 prevented the IL-10 protective effect abolishing the inhibiting effect of IL-10 on the generation of the Ca2+ synchronous spike. These findings point out to the leading role of GABAergic neurons in the development of posthypoxic hyperexcitability. We suggest that the reason for posthypoxic hyperexcitability in the network is a weakening of the inhibiting effect of GABAergic neurons. Activation of different signaling pathways leading to activation of PKB- and PKG-dependent phosphorylation in the neurons of this type represents a possible strategy to protect neurons from death during hypoxia. © 2014 Pleiades Publishing, Ltd.

引用

页码：125 / 135

页数：10

共 46 条

[1] Siesjo B.K., Calcium and ischemic brain damage, European Neurology, 25, SUPPL. 1, pp. 45-56, (1986)
[2] Choi D.W., Glutamate neurotoxicity in cortical cell culture is calcium dependent, Neuroscience Letters, 58, 3, pp. 293-297, (1985)
[3] Friedman L.K., Calcium: A role for neuroprotection and sustained adaptation, Molecular Interventions, 6, 6, pp. 315-329, (2006)
[4] Heurteaux C., Lauritzen I., Widmann C., Lazdunski M., Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning, Proc. Natl. Acad. Sci. USA, 92, pp. 4666-4670, (1995)
[5] Kumral A., Baskin H., Gokmen N., Yilmaz O., Genc K., Genc S., Tatli M.M., Duman N., Ozer E., Ozkan H., Selective inhibition of nitric oxide in hypoxic-ischemic brain model in newborn rats: Is it an explanation for the protective role of erythropoietin?, Biology of the Neonate, 85, 1, pp. 51-54, (2004)
[6] Bernaudin M., Tang Y., Reilly M., Petit E., Sharp F.R., Brain genomic response following hypoxia and re-oxygenation in the neonatal rat: Identification of genes that might contribute to hypoxia-induced ischemic tolerance, Journal of Biological Chemistry, 277, 42, pp. 39728-39738, (2002)
[7] Bergeron M., Gidday J.M., Yu A.Y., Semenza G.L., Ferriero D.M., Sharp F.R., Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain, Ann. Neurol., 48, pp. 285-296, (2000)
[8] Bond A., Lodge D., Hicks C.A., Ward M.A., O'Neill M.J., NMDA receptor antagonism, but not AMPA receptor antagonism attenuates induced ischaemic tolerance in the gerbil hippocampus, European Journal of Pharmacology, 380, 2-3, pp. 91-99, (1999)
[9] Godukhin O., Savin A., Kalemenev S., Levin S., Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: Involvement of ionotropic glutamate receptors and L-type Ca2+ channels, Neuropharmacology, 42, 4, pp. 459-466, (2002)
[10] Levin S.G., Godukhin O.V., Comparative roles of ATP-sensitive K+ channels and Ca 2+-activated BK+- channels in posthypoxic hyperexcitability and rapid hypoxic preconditioning in hippocampal CA1 pyramidal neurons in vitro, Neurosci. Lett., 461, pp. 90-94, (2009)

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