LAUSR

Abstract Aging increases the risk of abrupt declines in cognitive function after an event that triggers immune system activation (e.g. surgery, infection, or injury). This phenomenon is poorly understood, but rodent models may provide clues. We have previously shown that aging (24-mo-old) F344xBN rats generally do not show significant physical or cognitive impairments. However, their brains mount an exaggerated inflammatory response to signals triggered by a peripheral immune challenge (an intraperitoneal injection of Escherichia coli or laparotomy). Their hippocampal levels of the proinflammatory cytokine IL-1β are significantly elevated for at least 8 d, but generally less than 14 d, after infection or surgery. This IL-1β elevation is mirrored by prolonged deficits in a hippocampus-dependent long-term memory task. In contrast, young (3-mo-old) counterparts exhibit only transient elevations in IL-1β that drop to near baseline levels within 24 h. We previously demonstrated that theta burst–evoked late-phase long-term potentiation (L-LTP)—a BDNF-dependent form of synaptic plasticity—is impaired in hippocampal area CA1 of aged animals 4 d after infection. Also, levels of mature brain-derived neurotrophic factor (mBDNF)—the protein isoform required for stabilization of L-LTP—are reduced in hippocampal synaptoneurosomes of aged animals at the same time point. In this study, we investigated whether the deficits in L-LTP and mBDNF persist in parallel with the elevation in IL-1β and impairment in memory. This was the case, consistent with the idea that an exaggerated brain inflammatory response may compromise memory consolidation in part by altering availability of mBDNF to stabilize memory-related synaptic plasticity.