Peripheral administration of poly I:C leads to increased hippocampal amyloid-beta and cognitive deficits in a non-transgenic mouse.

Autor: Weintraub MK; Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Kranjac D; Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Eimerbrink MJ; Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Pearson SJ; Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Vinson BT; Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Patel J; Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Summers WM; Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Parnell TB; Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Boehm GW; Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA., Chumley MJ; Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA. Electronic address: m.chumley@tcu.edu.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2014 Jun 01; Vol. 266, pp. 183-7. Date of Electronic Publication: 2014 Mar 12.
DOI: 10.1016/j.bbr.2014.03.009
Abstrakt: 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.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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