Impairment of synaptic transmission by transient hypoxia in hippocampal slices: improved recovery in glutathione peroxidase transgenic mice.
There is increasing evidence that oxygen free radicals contribute to ischemic brain injury. It is unclear, however, to what extent specific antioxidant enzymes can prevent or reverse the impairment of synaptic function caused by transient hypoxia. In this study, we investigated in transgenic (Tg) mice whether a moderate increase in glutathione peroxidase-1 (GPx1) may improve the capacity of CA1 pyramidal cells to recover synaptic transmission after a short period of hypoxia in vitro. In control hippocampal slices, transient hypoxia (7-9 min) produced irreversible loss of excitatory postsynaptic potentials. Complete recovery of synaptic transmission was observed with homozygous Tg-MT-GPx-6 mice after reoxygenation, and, after repeated episodes of hypoxia, synaptic transmission was still viable in most Tg slices, in contrast to non-Tg slices. Moreover, hypoxic episodes abolished the capacity of hippocampal slices to generate long-term potentiation in area CA1 of control mice, whereas a significant extent of long-term potentiation expression was still preserved in Tg tissues. We also demonstrated that susceptibility to N-methyl-d-aspartate-mediated oxidative injury was reduced in Tg hippocampal slices. In conclusion, our results suggest that a moderate GPx increase can be sufficient to prevent irreversible functional damage produced by transient hypoxia in the hippocampus and to help maintain basic electrophysiological mechanisms involved in memory formation.
Furling
D
D
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Trois-Rivières, QC Canada G9A 5H7.
Ghribi
O
O
Lahsaini
A
A
Mirault
M E
ME
Massicotte
G
G
D000818:Animals; D015687:Cell Hypoxia; D005979:Glutathione Peroxidase / Q000235:genetics*; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D018384:Oxidative Stress; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D013870:Thiomalates / Q000494:pharmacology
D013870:Thiomalates; D016202:N-Methylaspartate; C046062:2-thiomalic acid; D005979:Glutathione Peroxidase