PROGRESSIVE DECLINE IN AVOIDANCE-LEARNING PARALLELED BY INFLAMMATORY NEURODEGENERATION IN TRANSGENIC MICE EXPRESSING INTERLEUKIN-6 IN THE BRAIN

Inflammation with expression of interleukin 6 (IL-6) in the brain occu rs in many neurodegentrative disorders, To better understand the role of IL-6 in such disorders, we examined performance in a learning task in conjunction with molecular and cellular neuropathology in transgeni c mice that express IL-6 chronically from astrocytes in the brain, Tra nsgenic mice exhibited dose- and age-related deficits in avoidance lea rning that closely corresponded with specific progressive neuropatholo gical changes. These results establish a link between the central nerv ous system expression of IL-6, inflammatory neurodegeneration, and a l earning impairment in transgenic mice, They suggest a critical role fo r a proinflammatory cytokine in the cognitive deficits and associated neuroinflammatory changes that have been documented in neurodegenerati ve diseases such as Alzheimer disease and AIDS.