βCTF-correlated burst of hippocampal TNFα occurs at a very early, pre-plaque stage in the TgCRND8 mouse model of Alzheimer's disease

在阿尔茨海默病的 TgCRND8 小鼠模型中,βCTF 相关的海马 TNFα 爆发发生在非常早期的斑块前阶段

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作者:Chelsea Cavanagh, Jessica Colby-Milley, David Bouvier, Mark Farso, Jean-Guy Chabot, Rémi Quirion, Slavica Krantic

Abstract

Tumor necrosis factor-alpha (TNFα) regulates neuronal excitability. We investigated whether alterations in the level of TNFα occur at a time point that precedes the reported seizure-associated hyperexcitability of hippocampal networks in pre-plaque models of Alzheimer's disease (AD). Western blot and ELISA experiments indicated a significant increase in hippocampal TNFα expression in 1-month-old TgCRND8 mice that correlated with levels of the β-C-terminal fragment (βCTF) of amyloid-β protein precursor. CD11b labeling indicated changes in microglial morphology toward an activated state, suggesting that these cells may be a putative source of the observed TNFα increase during this pre-symptomatic stage of AD-like pathology.

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