55. the Role of the Liver in E. Coli-Induced Memory Impairments in Aged Rats

Aged rats show a particular vulnerability to long-term memory impairments following a peripheral immune challenge. We have previously shown that aged rats infected with E. coli exhibit a long lasting hippocampal-dependent memory impairment, and an accompanying exaggerated cytokine response in the hippocampus. Interestingly, cytokines were not exaggeratedly elevated in serum or spleen samples. The lack of a long-lasting cytokine response in these peripheral samples suggested that the signal potentiating hippocampal cytokines was being generated from within the brain, and not coming from the periphery. Evidence from the present study however, suggests that the liver may be of significant importance because we show that pro-inflammatory cytokines in this peripheral organ are indeed potentiated in only aged and infected subjects. Young infected rats do not show this potentiation. Here, we examine the role of the liver in signaling the hippocampus following an immune challenge using both in vivo and ex vivo manipulations. Finally, we examine the directionality of that signal by blocking cytokine action in the brain with IL-1 receptor antagonist, or by blocking cytokine action in the liver by depleting liver macrophages with clodronate-encapsulated liposomes either before, or shortly after infection.