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

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• 作者：Francisco Capani ; Gustavo Ezequiel Saraceno ; Valeria Botti ; Laura Aon-Bertolino ; Diê ; go Madureira de Oliveira ; George Barreto ; Pablo Galeano ; Lis ; ro Diego Giraldez-Alvarez ; Hé ; ctor Coirini
• 关键词：Postsynaptic density ; Hypoxia ; Neostriatum ; Ubiquitin ; Hypothermia ; Neuroprotection ; Perinatal asphyxia
• 刊名：Experimental Neurology
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：219
• 期：2
• 页码：404-413
• 全文大小：2552 K

文摘

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.