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 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.
Tanabe
Mitsuo
M
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. tanabemi@pharm.kitasato-u.ac.jp
Nitta
Azusa
A
Ono
Hideki
H
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D013331:Strychnine / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013654:Taurine / Q000494:pharmacology
D018696:Neuroprotective Agents; D018009:Receptors, Glycine; D013654:Taurine; D013331:Strychnine; D005998:Glycine