Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related neurodegenerative deficits.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 Oct 2024
11 Oct 2024
Historique:
received:
14
08
2023
accepted:
04
10
2024
medline:
12
10
2024
pubmed:
12
10
2024
entrez:
11
10
2024
Statut:
epublish
Résumé
One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinson's, Alzheimer's and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal models because common laboratory species, such as rodents, do not produce neuromelanin. Here we generate a tissue-specific transgenic mouse, termed tgNM, that mimics the human age-dependent brain-wide distribution of neuromelanin within catecholaminergic regions, based on the constitutive catecholamine-specific expression of human melanin-producing enzyme tyrosinase. We show that, in parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model could help explore new research avenues in brain aging and neurodegeneration.
Identifiants
pubmed: 39394193
doi: 10.1038/s41467-024-53168-7
pii: 10.1038/s41467-024-53168-7
doi:
Substances chimiques
Melanins
0
neuromelanin
0
Catecholamines
0
Monophenol Monooxygenase
EC 1.14.18.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8819Informations de copyright
© 2024. The Author(s).
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