title: βCTF-correlated burst of hippocampal TNFα occurs at a very early, pre-plaque stage in the TgCRND8 mouse model of Alzheimer's disease.
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.
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Verdun, Montréal, QC, Canada.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Cavanagh
authors.forename: Jessica
authors.initials: J
authors.lastname: Colby-Milley
authors.forename: David
authors.initials: D
authors.lastname: Bouvier
authors.forename: Mark
authors.initials: M
authors.lastname: Farso
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Chabot
authors.forename: Rémi
authors.initials: R
authors.lastname: Quirion
authors.forename: Slavica
authors.initials: S
authors.lastname: Krantic
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C491049:Aif1 protein, mouse; D016564:Amyloid beta-Protein Precursor; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha