IL-6 trans-signaling in the brain influences the behavioral and physio-pathological phenotype of the Tg2576 and 3xTgAD mouse models of Alzheimer's disease.
Alzheimer Disease
/ immunology
Amyloid beta-Peptides
/ metabolism
Amyloid beta-Protein Precursor
/ genetics
Amyloidosis
/ pathology
Animals
Brain
/ metabolism
Cerebral Cortex
/ metabolism
Cytokines
/ metabolism
Disease Models, Animal
Female
Hippocampus
/ metabolism
Interleukin-6
/ genetics
Mice
Mice, Inbred Strains
Mice, Transgenic
Neurofibrillary Tangles
/ metabolism
Peptide Fragments
Plaque, Amyloid
/ pathology
Signal Transduction
Alzheimer’s disease
Amyloidosis
Behavior
IL-6
IL-6 trans-signaling
Survival
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
07
02
2019
revised:
09
07
2019
accepted:
07
08
2019
pubmed:
12
8
2019
medline:
26
8
2020
entrez:
12
8
2019
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is the most commonly diagnosed dementia but its underlying pathological mechanisms still unclear. Neuroinflammation and secretion of cytokines such as interleukin-6 (IL-6) accompany the main hallmarks of the disease: amyloid plaques and neurofibrillary tangles. In this study, we analyzed the role of IL-6 trans-signaling in two mouse models of AD, Tg2576 and 3xTg-AD mice. The inhibition of IL-6 trans-signaling partially rescued the AD-induced mortality in females of both models. Before amyloid plaques deposition, it reversed AD-induced changes in exploration and anxiety (but did not affect locomotion) in Tg2576 female mice. However, after plaque deposition the only behavioral trait affected by the inhibition of IL-6 trans-signaling was locomotion. Results in the Morris water maze suggest that cognitive flexibility was reduced by the blocking of the IL-6 trans-signaling in young and old Tg2576 female mice. The inhibition of IL-6 trans-signaling also decreased amyloid plaque burden in cortex and hippocampus, and Aβ
Identifiants
pubmed: 31401302
pii: S0889-1591(19)30150-3
doi: 10.1016/j.bbi.2019.08.005
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Cytokines
0
Interleukin-6
0
Peptide Fragments
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-159Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.