title: Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia.
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.
authors: 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@fmed.uba.ar
authors: Francisco
authors: F
authors: Capani
authors: Gustavo Ezequiel
authors: GE
authors: Saraceno
authors: Valeria
authors: V
authors: Botti
authors: Laura
authors: L
authors: Aon-Bertolino
authors: Diêgo Madureira
authors: DM
authors: de Oliveira
authors: George
authors: G
authors: Barreto
authors: Pablo
authors: P
authors: Galeano
authors: Lisandro Diego
authors: LD
authors: Giraldez-Alvarez
authors: Héctor
authors: H
authors: Coirini
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D064026:Calbindins; D004195:Disease Models, Animal; D055032:Electron Microscope Tomography / Q000379:methods; D005260:Female; D007036:Hypothermia, Induced / Q000379:methods*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D014452:Ubiquitins / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D014452:Ubiquitins; D005680:gamma-Aminobutyric Acid