Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia.
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.
Capani
Francisco
F
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
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
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
D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D014452:Ubiquitins; D005680:gamma-Aminobutyric Acid