Weintraub Marielle K, Kranjac Dinko, Eimerbrink Micah J, Pearson Scott J, Vinson Ben T, Patel Jigna, Summers Whitney M, Parnell Thomas B, Boehm Gary W, Chumley Michael J
Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
Behav Brain Res. 2014 Jun 1;266:183-7. doi: 10.1016/j.bbr.2014.03.009. Epub 2014 Mar 12.
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.
阿尔茨海默病（AD）是一种以神经元和行为退化为特征的进行性疾病。AD的两个标志性病理特征是β-淀粉样蛋白（Aβ）斑块和神经原纤维缠结，这种病理特征的存在会限制细胞间通讯，导致认知缺陷和神经元细胞死亡。尽管最初认为Aβ斑块会导致认知缺陷，但更简单形式的Aβ，如单体、二聚体、四聚体和寡聚体，也已被证明具有神经毒性。此外，慢性炎症也与这些AD相关病理的发生和发展有关。本研究旨在通过给予聚肌苷酸:聚胞苷酸（poly I:C），一种病毒模拟物，来进一步了解外周炎症诱导的AD样病理。小鼠连续7天每天腹腔注射一次poly I:C或生理盐水。接受poly I:C的动物的海马组织中Aβ₁₋₄₂肽水平显著更高。即使在确保潜在的疾病行为不会混淆认知测试之后，我们发现接受poly I:C的动物在海马依赖性情境恐惧条件反射范式中表现出显著的认知缺陷。这些结果证实了我们的假设，即外周炎症可导致海马Aβ水平升高及相关的认知缺陷。
