Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia

Francisco Capani, Gustavo Ezequiel Saraceno, Valeria Botti, Laura Aon-Bertolino, Diêgo Madureira de Oliveira, George Barreto, Pablo Galeano, Lisandro Diego Giraldez-Alvarez, Héctor Coirini

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.

Original languageEnglish
Pages (from-to)404-413
Number of pages10
JournalExperimental Neurology
Volume219
Issue number2
DOIs
Publication statusPublished - Oct 2009
Externally publishedYes

Keywords

  • Hypothermia
  • Hypoxia
  • Neostriatum
  • Neuroprotection
  • Perinatal asphyxia
  • Postsynaptic density
  • Ubiquitin

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