Grant: Operating Grant

When people or animals get an infection, the body responds with an immune response that recognizes specific molecules on the infectious agent (eg bacterium or virus) and causes a number of alterations in the body's physiology and behavior that helps to fight the infection. There are synthetic molecules that can be given to mimic the infection, allowing us to study this process without making the animals truly 'infectious'. We are interested in what happen when a newborn has an infection and in how this affects the animal as an adult. Previously we found that 14d old rats that were given a mild 'experimental' inflammation responded, as adults with a markedly reduced inflammatory response. In addition, a number of other changes in the brain were observed, including altered pain sensitivity, altered brain susceptibility to stroke trauma and altered brain excitability (meaning that they were more susceptible to seizures). These findings are of obvious clinical interest and have prompted the preset application in which we will try to identify the underlying cellular and neurochemical mechanisms that underlies these alterations. Our work will employ behavioral, neurochemical and electrophysiological approaches to test specific hypotheses concerning the involvement of specific molecules and alterations in specific neuronal ion channels and neurotransmitter receptors. We will determine if there are long term changes in genes that code for specific molecules. Finally we will employ a number of interventions, including behavioral enrichment and pharmacological treatments to see if we can reverse the effects of this 'neonatal programming' by inflammation.