title: Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice.
abstract: Neuroinflammatory conditions such as traumatic brain injury, aging, Alzheimer's disease, and Down syndrome are often associated with cognitive dysfunction. Much research has targeted inflammation as a causative mediator of these deficits, although the diverse cellular and molecular changes that accompany these disorders obscure the link between inflammation and impaired memory. Therefore, we used a transgenic mouse model with a dormant human IL-1beta excisional activation transgene to direct overexpression of IL-1beta with temporal and regional control. Two weeks of hippocampal IL-1beta overexpression impaired long-term contextual and spatial memory in both male and female mice, while hippocampal-independent and short-term memory remained intact. Human IL-1beta overexpression activated glia, elevated murine IL-1beta protein and PGE(2) levels, and increased pro-inflammatory cytokine and chemokine mRNAs specifically within the hippocampus, while having no detectable effect on inflammatory mRNAs in the liver. Sustained neuroinflammation also reduced basal and conditioning-induced levels of the plasticity-related gene Arc.
authors.affiliation: Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Hein
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Stasko
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Matousek
authors.forename: Jonah J
authors.initials: JJ
authors.lastname: Scott-McKean
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
authors.forename: John A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: Alberto C S
authors.initials: AC
authors.lastname: Costa
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D003213:Conditioning, Psychological; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D005239:Fear / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000276:immunology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013028:Space Perception / Q000502:physiology*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D014765:Viral Vaccines; C092069:activity regulated cytoskeletal-associated protein; D015232:Dinoprostone