Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial memory.
Glial activation and neuroinflammation occur in neurodegenerative disease and brain injury, however their presence in normal brain aging suggests that chronic neuroinflammation may be a factor in age-related dementia. Few studies have investigated the impact of sustained elevation of hippocampal interleukin-1beta, a pro-inflammatory cytokine upregulated during aging and Alzheimer's disease, on cognition in mice. We utilized the IL-1beta(XAT) transgenic mouse to initiate bilateral hippocampal overexpression of interleukin-1beta to determine the influence of sustained neuroinflammation independent of disease pathology. Fourteen days following transgene induction, adult male and female IL-1beta(XAT) mice were tested on non-spatial and spatial versions of the Morris water maze. For the spatial component, one retention trial was conducted 48 h after completion of a 3 day acquisition protocol (eight trials per day). Induction of IL-1beta did not impact non-spatial learning, but was associated with delayed acquisition and decreased retention of the spatial task. These behavioral impairments were accompanied by robust reactive gliosis and elevated mRNA expression of inflammatory genes in the hippocampus. Our results suggest that prolonged neuroinflammation response per se may impact mnemonic processes and support the future application of IL-1beta(XAT) transgenic mice to investigate chronic neuroinflammation in age- and pathology-related cognitive dysfunction.
Moore
A H
AH
Department of Biology, Santa Clara University, Santa Clara, CA 95053, USA. amoore@carleton.edu
Wu
M
M
Shaftel
S S
SS
Graham
K A
KA
O'Banion
M K
MK
D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D013037:Spatial Behavior
D053583:Interleukin-1beta