Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice.
5XFAD
Alzheimer's disease
CP: Immunology
CP: Neuroscience
astrocyte
behavior
mast cell
meninges
microglia
neuroimmune interaction
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 09 2023
26 09 2023
Historique:
received:
13
07
2022
revised:
20
06
2023
accepted:
30
08
2023
medline:
13
11
2023
pubmed:
15
9
2023
entrez:
15
9
2023
Statut:
ppublish
Résumé
Emerging evidence suggests that peripheral immune cells contribute to Alzheimer's disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice with mast cell-deficient strains and observed the effects on AD-related neuropathology and cognitive impairment. We found that mast cell depletion improved contextual fear conditioning in 5XFAD mice without affecting cued fear conditioning, anxiety-like behavior, or amyloid burden. Furthermore, mast cell depletion led to an upregulation of transcriptomic signatures for putatively protective disease-associated microglia and resulted in reduced markers indicative of reactive astrocytes. We hypothesize a system of bidirectional communication between dural mast cells and the brain, where mast cells respond to signals from the brain environment by expressing immune-regulatory mediators, impacting cognition and glial cell function. These findings highlight mast cells as potential therapeutic targets for AD.
Identifiants
pubmed: 37713312
pii: S2211-1247(23)01153-1
doi: 10.1016/j.celrep.2023.113141
pmc: PMC10634538
mid: NIHMS1933923
pii:
doi:
Substances chimiques
Immunologic Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
113141Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK040561
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG000222
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.E.T. is a consultant to and shareholder in AZTherapeutics. R.I.S. is a shareholder in Feromics.
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