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 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.
Heyser
C J
CJ
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Masliah
E
E
Samimi
A
A
Campbell
I L
IL
Gold
L H
LH
D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry; D003072:Cognition Disorders / Q000209:etiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000523:psychology*; D006579:Heterozygote; D006624:Hippocampus / Q000737:chemistry; D007091:Image Processing, Computer-Assisted; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic
D015850:Interleukin-6