The causes of many cognitive and memory disturbances are poorly understood. However, many of these disturbances (e.g., Alzheimer's disease, AIDS dementia, autoimmune disease, viral diseases such as Borna virus, normal aging, cancer and cancer chemotherapy) are associated with elevated levels of peripheral and/or brain cytokines, which are immune products released in response to infection. Some researchers have speculated that cognitive impairments are part of the """"""""sickness pattern"""""""" produced by cytokines and that increased brain levels of a particular cytokine, IL-1beta, may play a key role in the production of these phenomena. However, the hypothesis that brain IL-1beta, or other cytokines produce cognitive/memory disturbances has received little systematic attention. The goal of this proposal is to systematically explore the implications of this hypothesis. We will do this by building on our past work to (a) determine if IL-1beta, impairs long-term memory consolidation on a range of tasks that depend on the hippocampus, (b) determine if IL-1beta, also impairs short-term memory, (c) determine if such memory impairments can be produced by naturally occurring conditions that induce IL-1beta, in the hippocampus such as infection, and (d) examine the hypothesis that IL-1beta, produces its effects on memory by its influence on brain derived neurotrophic factor (BDNF). Thus, the proposed research will contribute to an understanding of disorders of memory, the operation of IL-1beta, in the brain, and the mechanisms that underlie learning and memory.
