Seed-induced Aβ deposition alters neuronal function and impairs olfaction in a mouse model of Alzheimer's disease.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
09
04
2021
accepted:
27
06
2022
revised:
22
06
2022
pubmed:
23
7
2022
medline:
7
12
2022
entrez:
22
7
2022
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) which ultimately forms plaques. These Aβ deposits can be induced in APP transgenic mouse models by prion-like seeding. It has been widely accepted that anosmia and hyposmia occur during the early stages of AD, even before cognitive deficits are present. In order to determine the impact of seed-induced Aβ deposits on olfaction, we performed intracerebral injections of seed-competent brain homogenate into the olfactory bulb of young pre-depositing APP transgenic mice. Remarkably, we observed a dramatic olfactory impairment in those mice. Furthermore, the number of newborn neurons as well as the activity of cells in the mitral cell layer was decreased. Notably, exposure to an enriched environment reduced Aβ seeding, vivified neurogenesis and most importantly reversed olfactory deficits. Based on our findings, we conclude that altered neuronal function as a result of induced Aβ pathology might contribute to olfactory dysfunction in AD.
Identifiants
pubmed: 35869271
doi: 10.1038/s41380-022-01686-5
pii: 10.1038/s41380-022-01686-5
pmc: PMC9718674
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4274-4284Informations de copyright
© 2022. The Author(s).
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