en
Scientific article
English

Remodeling of hippocampal synaptic networks by a brief anoxia-hypoglycemia

Published inThe Journal of neuroscience, vol. 22, no. 8, p. 3108-3116
Publication date2002
Abstract

Cerebral ischemia is a major cause of brain dysfunction. Using a model of delayed death induced by a brief, transient oxygen and glucose deprivation, we studied here how this affected the structural organization of hippocampal synaptic networks. We report that brief anoxic-hypoglycemic episodes rapidly modified the structure of synapses. This was characterized, at the electron microscopic level, by a transient increase in the proportion of perforated synapses, followed after 2 hr by an increase in images of multiple synapse boutons. These changes were considerable because 10-20% of all synapses were affected. This structural remodeling was correlated by three kinds of modifications observed using two-photon confocal microscopy: the growth of filopodia, occurring shortly (5-20 min) after anoxia-hypoglycemia, enlargements of existing spines, and formation of new spines, both seen mainly 20-60 min after the insult. All of these structural changes were calcium and NMDA receptor dependent and thus reproduced, to a larger scale, those associated with synaptic plasticity. Concomitantly and related to the severity of anoxia-hypoglycemia, we could also observe spine loss and images of spine, dendrite, or presynaptic terminal swellings that evolved up to membrane disruption. These changes were also calcium dependent and reduced by NMDA receptor antagonists. Thus, short anoxic-hypoglycemic episodes, through NMDA receptor activation and calcium influx, resulted in a profound structural remodeling of synaptic networks, through growth, formation, and elimination of spines and synapses.

Keywords
  • Animals
  • Cell Death
  • Cell Hypoxia
  • Cell Surface Extensions/ultrastructure
  • Coloring Agents
  • Dendrites/ultrastructure
  • Excitatory Amino Acid Antagonists/pharmacology
  • Excitatory Postsynaptic Potentials
  • Hippocampus/cytology/ physiopathology
  • Hypoglycemia/ physiopathology
  • Ischemic Attack, Transient/ physiopathology
  • Nerve Net/ physiopathology
  • Neurons/drug effects/ultrastructure
  • Patch-Clamp Techniques
  • Rats
  • Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
  • Synapses/ metabolism/ultrastructure
  • Synaptic Transmission/drug effects
  • Time Factors
Citation (ISO format)
JOURDAIN, Pascal et al. Remodeling of hippocampal synaptic networks by a brief anoxia-hypoglycemia. In: The Journal of neuroscience, 2002, vol. 22, n° 8, p. 3108–3116.
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ISSN of the journal0270-6474
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