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

Exp Neurol. 2009 Oct;219(2):404-13. doi: 10.1016/j.expneurol.2009.06.007. Epub 2009 Jun 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Calbindins
  • Disease Models, Animal
  • Electron Microscope Tomography / methods
  • Female
  • Hypothermia, Induced / methods*
  • Hypoxia, Brain* / metabolism
  • Hypoxia, Brain* / pathology
  • Hypoxia, Brain* / therapy
  • Male
  • Microscopy, Immunoelectron / methods
  • Neostriatum / metabolism*
  • Neostriatum / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / ultrastructure
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • S100 Calcium Binding Protein G / metabolism
  • Subcellular Fractions / metabolism
  • Subcellular Fractions / ultrastructure
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Time Factors
  • Ubiquitins / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Calbindins
  • S100 Calcium Binding Protein G
  • Ubiquitins
  • gamma-Aminobutyric Acid