title: Peripheral administration of poly I:C leads to increased hippocampal amyloid-beta and cognitive deficits in a non-transgenic mouse.
abstract: Alzheimer's disease (AD) is a progressive disorder characterized by neuronal and behavioral deterioration. Two hallmark pathologies of AD are amyloid-beta (Aβ) plaques and neurofibrillary tangles, and the presence of such pathology can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although Aβ plaques were originally thought to cause the cognitive deficits, more simple forms of Aβ, such as monomers, dimers, tetramers and oligomers, have also been shown to be neurotoxic. Moreover, chronic inflammation has also been implicated in the onset and progression of these AD-related pathologies. The current study was designed to further our understanding of peripheral inflammation-induced AD-like pathology, by administering polyinosinic:polycytidylic acid (poly I:C), a viral mimetic. Mice were administered intraperitoneal injections of poly I:C or saline once daily for 7 consecutive days. Hippocampal tissue from animals receiving poly I:C contained significantly higher levels of the Aβ₁₋₄₂ peptide. Even after ensuring that potential sickness behavior could not confound cognitive testing, we found that animals administered poly I:C displayed significant cognitive deficits in the hippocampus-dependent contextual fear conditioning paradigm. These results confirm our hypothesis that peripheral inflammation can lead to increased levels of hippocampal-Aβ and associated cognitive deficits.
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Marielle K
authors.initials: MK
authors.lastname: Weintraub
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Dinko
authors.initials: D
authors.lastname: Kranjac
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Eimerbrink
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Pearson
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Ben T
authors.initials: BT
authors.lastname: Vinson
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Jigna
authors.initials: J
authors.lastname: Patel
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Summers
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Parnell
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Boehm
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA. Electronic address: m.chumley@tcu.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chumley
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D007369:Interferon Inducers / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism*; D011070:Poly I-C / Q000633:toxicity*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D007369:Interferon Inducers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D011070:Poly I-C
keywords: Alzheimer's disease; Amyloid-beta; Cognition; Cytokines; Poly I:C