D. Furling et al., Impairment of synaptic transmission by transient hypoxia in hippocampal slices: Improved recovery in glutathione peroxidase transgenic mice, P NAS US, 97(8), 2000, pp. 4351-4356
Citations number
38
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
There is increasing evidence that oxygen free radicals ischemic brain injur
y. 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 m
oderate increase in glutathione peroxidase-1 (CPx1) may improve the capacit
y of CA1 pyramidal cells to recover synaptic transmission after a short per
iod 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 n
on-Tg slices. Moreover, hypoxic episodes abolished the capacity of hippocam
pal 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-met
hyl-o-aspartate-mediated oxidative injury was reduced in Tg hippocampal sli
ces. 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 electro-physiologica
l mechanisms involved in memory formation.