Progressive Decline in Avoidance Learning Paralleled by Inflammatory Neurodegeneration in Transgenic Mice Expressing Interleukin 6 in the Brain

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-02, Vol.94 (4), p.1500-1505
• Main Authors: Heyser, Charles J., Masliah, Eliezer, Samimi, Ana, Campbell, Iain L., Gold, Lisa H.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Astrocytes - metabolism; Avoidance Learning - physiology; Biochemistry; Biological Sciences; Brain; Brain - cytology; Brain - metabolism; Brain damage; Cerebral Cortex - chemistry; Cognition Disorders - etiology; Dementia; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - psychology; Heterozygote; Hippocampus; Hippocampus - chemistry; Image Processing, Computer-Assisted; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukins; Interneurons; Learning; Maze Learning - physiology; Mice; Mice, Transgenic; Neurology; Neurons; Observational learning; Pathology; Rodents; Transgenic animals
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.4.1500

Inflammation with expression of interleukin 6 (IL-6) in the brain occurs in many neurodegenerative 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 transgenic mice that express IL-6 chronically from astrocytes in the brain. Transgenic mice exhibited dose- and age-related deficits in avoidance learning that closely corresponded with specific progressive neuropathological changes. These results establish a link between the central nervous system expression of IL-6, inflammatory neurodegeneration, and a learning impairment in transgenic mice. They suggest a critical role for a proinflammatory cytokine in the cognitive deficits and associated neuroinflammatory changes that have been documented in neurodegenerative diseases such as Alzheimer disease and AIDS.