TY - JOUR
T1 - Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia
AU - Capani, Francisco
AU - Saraceno, Gustavo Ezequiel
AU - Botti, Valeria
AU - Aon-Bertolino, Laura
AU - Madureira de Oliveira, Diêgo
AU - Barreto, George
AU - Galeano, Pablo
AU - Giraldez-Alvarez, Lisandro Diego
AU - Coirini, Héctor
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Hypothermia
KW - Hypoxia
KW - Neostriatum
KW - Neuroprotection
KW - Perinatal asphyxia
KW - Postsynaptic density
KW - Ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=69749087786&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2009.06.007
DO - 10.1016/j.expneurol.2009.06.007
M3 - Article
C2 - 19555686
AN - SCOPUS:69749087786
SN - 0014-4886
VL - 219
SP - 404
EP - 413
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -