Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related neurodegenerative deficits

Ariadna Laguna, Núria Peñuelas, Marta Gonzalez-Sepulveda, Alba Nicolau, Sébastien Arthaud, Camille Guillard-Sirieix, Marina Lorente-Picón, Joan Compte, Lluís Miquel-Rio, Helena Xicoy, Jiong Liu, Annabelle Parent, Thais Cuadros, Jordi Romero-Giménez, Gemma Pujol, Lydia Giménez-Llort, Patrice Fort, Analia Bortolozzi, Iria Carballo-Carbajal and Miquel Vila ()
Additional contact information
Ariadna Laguna: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Núria Peñuelas: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Marta Gonzalez-Sepulveda: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Alba Nicolau: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Sébastien Arthaud: SLEEP team “Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil”
Camille Guillard-Sirieix: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Marina Lorente-Picón: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Joan Compte: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Lluís Miquel-Rio: Spanish National Research Council (CSIC); Center for Networked Biomedical Research on Mental Health (CIBERSAM)
Helena Xicoy: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Jiong Liu: SLEEP team “Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil”
Annabelle Parent: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Thais Cuadros: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Jordi Romero-Giménez: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Gemma Pujol: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Lydia Giménez-Llort: Institut de Neurociències-Autonomous University of Barcelona (INc-UAB)
Patrice Fort: SLEEP team “Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil”
Analia Bortolozzi: Spanish National Research Council (CSIC); Center for Networked Biomedical Research on Mental Health (CIBERSAM)
Iria Carballo-Carbajal: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
Miquel Vila: Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53168-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53168-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53168-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().