Ammonia tolerant, diapausing copepods as model system for hepatic encephalopathy
Hepathic encephalopathy (HE) is a common and potentially life threatening disease that results from impaired liver function or liver failure. Liver failure causes high plasma ammonia levels, which have been associated with swelling of glial cells (astrocytes), brain edema, and, subsequently, severe neurological damage due to increased intracranial pressure and mortality. While detrimental plasma ammonium levels in mammals typically are <1 mM, recent findings indicate that diapausing copepods accumulate plasma ammonium in excess of 200 mM for months. Owing to similarities in basic central nervous system (CNS) architecture, we believe that understanding mechanisms of high ammonia tolerance in copepods can aid in a better understanding of HE pathophysiology and contribute towards improved disease treatment in humans. We propose to use a range of techniques to characterize ammonia detoxification pathways, brain ultrastructure and brain functional impairment in copepods exposed to high plasma ammonia concentrations. This research is important for understanding diapause biology in copepods, the most important zooplankton group, and will help us learn more about how cells cope with high ammonium concentrations.
