Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus

Recent evidence indicates that strychnine-sensitive glycine receptors are located in upper brain regions including the hippocampus. Because of excitatory effects of glycine via facilitation of NMDA-receptor function, however, the net effects of increased extracellular glycine on neuronal excitabilit...

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Main Authors: Mitsuo Tanabe, Azusa Nitta, Hideki Ono
Format: Article
Language:English
Published: Elsevier 2010-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319309053
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spelling doaj-d69477cd84bc481f81312937c1801f922020-11-25T01:51:04ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011134378386Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the HippocampusMitsuo Tanabe0Azusa Nitta1Hideki Ono2Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; Present address: Laboratory of Pharmacology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Corresponding author. tanabemi@pharm.kitasato-u.ac.jpLaboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanLaboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanRecent evidence indicates that strychnine-sensitive glycine receptors are located in upper brain regions including the hippocampus. Because of excitatory effects of glycine via facilitation of NMDA-receptor function, however, the net effects of increased extracellular glycine on neuronal excitability in either physiological or pathophysiological conditions are mostly unclear. Here, we addressed the potential neuroprotective effect of either exogenous application of glycine and taurine, which are both strychnine-sensitive glycine-receptor agonists, or an endogenous increase of glycine via blockade of glycine transporter 1 (GlyT1) by assessing their ability to facilitate the functional recovery of field excitatory postsynaptic potentials (fEPSPs) after termination of brief oxygen/glucose deprivation (OGD) in the CA1 region in mouse hippocampal slices. Glycine and taurine promoted restoration of the fEPSPs after reperfusion, but this was never observed in the presence of strychnine. Interestingly, glycine and taurine appeared to generate neuroprotective effects only at their optimum concentration range. By contrast, blockade of GlyT1 by N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl]sarcosine or sarcosine did not elicit significant neuroprotection. These results suggest that activation of strychnine-sensitive glycine receptors potentially produces neuroprotection against metabolic stress such as OGD. However, GlyT1 inhibition is unlikely to elicit a sufficient increase in the extracellular level of glycine to generate neuroprotection. Keywords:: oxygen/glucose deprivation, neuroprotection, glycine, strychnine-sensitive glycine receptor, glycine transporterhttp://www.sciencedirect.com/science/article/pii/S1347861319309053
collection DOAJ
language English
format Article
sources DOAJ
author Mitsuo Tanabe
Azusa Nitta
Hideki Ono
spellingShingle Mitsuo Tanabe
Azusa Nitta
Hideki Ono
Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus
Journal of Pharmacological Sciences
author_facet Mitsuo Tanabe
Azusa Nitta
Hideki Ono
author_sort Mitsuo Tanabe
title Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus
title_short Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus
title_full Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus
title_fullStr Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus
title_full_unstemmed Neuroprotection via Strychnine-Sensitive Glycine Receptors During Post-ischemic Recovery of Excitatory Synaptic Transmission in the Hippocampus
title_sort neuroprotection via strychnine-sensitive glycine receptors during post-ischemic recovery of excitatory synaptic transmission in the hippocampus
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2010-01-01
description Recent evidence indicates that strychnine-sensitive glycine receptors are located in upper brain regions including the hippocampus. Because of excitatory effects of glycine via facilitation of NMDA-receptor function, however, the net effects of increased extracellular glycine on neuronal excitability in either physiological or pathophysiological conditions are mostly unclear. Here, we addressed the potential neuroprotective effect of either exogenous application of glycine and taurine, which are both strychnine-sensitive glycine-receptor agonists, or an endogenous increase of glycine via blockade of glycine transporter 1 (GlyT1) by assessing their ability to facilitate the functional recovery of field excitatory postsynaptic potentials (fEPSPs) after termination of brief oxygen/glucose deprivation (OGD) in the CA1 region in mouse hippocampal slices. Glycine and taurine promoted restoration of the fEPSPs after reperfusion, but this was never observed in the presence of strychnine. Interestingly, glycine and taurine appeared to generate neuroprotective effects only at their optimum concentration range. By contrast, blockade of GlyT1 by N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl]sarcosine or sarcosine did not elicit significant neuroprotection. These results suggest that activation of strychnine-sensitive glycine receptors potentially produces neuroprotection against metabolic stress such as OGD. However, GlyT1 inhibition is unlikely to elicit a sufficient increase in the extracellular level of glycine to generate neuroprotection. Keywords:: oxygen/glucose deprivation, neuroprotection, glycine, strychnine-sensitive glycine receptor, glycine transporter
url http://www.sciencedirect.com/science/article/pii/S1347861319309053
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