The role of the thioredoxin family proteins in a murine model of perinatal asphyxia

AON-BERTOLINO, MARÍA LAURA; ROMERO, JUAN IGNACIO; SARACENO, GUSTAVO EZEQUIEL; GALEANO, PABLO; LILLIG, CHRISTOPHER HORST; CAPANI, FRANCISCO

Alejandría

Conferencia; BioVisionAlexandria 2010; 2010

Bibliotheca Alexandrina and World Life Sciences Forum, BioVision

Background- Thioredoxins (Trxs), Glutaredoxins (Grxs) and Peroxiredoxins (Prxs) are one of the major antioxidant systems in the cell, playing an important role in the maintenance of intracellular redox homeostasis. Although these proteins have been thoroughly studied in numerous cellular and animal models mimicking human diseases, such as cerebral ischemia and neurodegenerative disorders, any systematic information in perinatal asphyxia is still available. Long term cerebral disabilities associated with perinatal asphyxia are mediated by active processes, which lead to the over production of reactive oxygen species (ROS) in part caused by glutamatergic-mediated increases in intracellular calcium concentration and subsequent tissue damage. Previous studies reported chronic alterations in neurotransmission in rat neocortex and neostriatum after 19 minutes of asphyxia. Objective- The aim of this work was to study the presence and distribution of Trxs, Grxs and Prxs in specific areas of pup rat brains submitted to perinatal asphyxia. Methods- Asphyxia was induced by immersing foetuses-containing uterine horns, removed from ready-to-deliver Sprague-Dawley rats, into a water bath at 37 ºC for 19 min. Control subjects (CTL) were born by vaginal delivery (see further details in Capani et al., 2009; Saraceno et al., 2010). At 30 min, 1, 2, 4, 6, 12, 18, 24, and 72 hours rats were sacrificed, brains removed and processed for immunohistochemistry and Western Blot. Results- We have observed some remarkable differential distribution of Trxs, Grxs and Prxs in the most vulnerable areas of the brain to hypoxia-ischemia (Hippocampus, Substantia nigra, Striatum, Cortex, Cerebellum, and Mesencephalon), as well as in different cell types (neurons, neurites, and glia cells) at different asphyctic time. Conclusions- The demonstration of the presence and expression of these proteins in specific cell types and regions of the pup rat brain that suffered from perinatal asphyxia gave us an important morphological statement to study later, some of the molecular mechanisms involved in the pathogenesis of brain ischemia. Such studies will facilitate our understanding of how Thioredoxin family proteins may modulate newborn diseases via redox regulation during early periods of life