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

Full 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.

Author information

Author/s: Capani, Francisco (F); Saraceno, Gustavo Ezequiel (GE); Botti, Valeria (V); Aon-Bertolino, Laura (L); de Oliveira, Diêgo Madureira (DM); Barreto, George (G); Galeano, Pablo (P); Giraldez-Alvarez, Lisandro Diego (LD); Coirini, Héctor (H);

Affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Buenos Aires, Argentina. fcapani(-atsign-)fmed.uba.ar

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Experimental neurology (Exp Neurol), published in United States. (Language: eng)

Reference: 2009-Oct; vol 219 (issue 2) : pp 404-13

Dates: Created 2009/09/14; Completed 2009/09/29;

PMID: 19555686, status: MEDLINE (last retrieval date: 9/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.