Meeting Abstract

S9.2  Tuesday, Jan. 6  Postnatal inflammation programs adult physiology PITTMAN, Quentin J; University of Calgary pittman@ucalgary.ca

The perinatal environment can be critical in programming many aspects of adult physiology, well being and susceptibility to disease. Increasing evidence now suggests that neuroimmune stress at crucial development periods can permanently alter the animals physiology. We have obtained compelling evidence that an inflammation induced by lipopolysaccharide (LPS) in 2 week old postnatal rat pups causes a long lasting programming of the neuroimmune response; this includes reduced fever, COX-2 activation and hyperalgesia to a subsequent induction of inflammation as an adult. Interestingly, associated behavioral (reduced activity, anorexia, anhedonia and reduced social interactions) are unchanged. The reduced fever in the adult is associated with reduced plasma cytokines, but with an elevation in circulating corticosterone (CORT) after LPS. The elevated CORT is responsible for the reduced responses and occurs because of increased secretion of of liver-derived prostaglandin. Postnatal LPS also causes a host of other long term alterations in the brain even in the absence of a subsequent immune challenge. Postnatal LPS treatment causes long term alterations in specific neurotransmitter receptor mRNA and greater neuronal loss after global cerebral ischemia or seizures as adults. These animals also display increased neuronal excitability, as adults, through mechanisms strongly dependent upon brain TNFalpha. These changes are associated with increased pain sensitivity, differences in memory performance, and in anxiety-like behavior, but no changes in weight. There are long term increases in basal brain and spinal cord COX-2 levels, but the relationship between the neurochemical changes and any of the alterations in the physiology and behavior are currently unknown.