Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related neurodegenerative deficits
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.
Authors
- Camille Guillard-Sirieix (ORCID: https://orcid.org/0000-0002-2645-1892)
- Marta González-Sepúlveda (ORCID: https://orcid.org/0000-0002-5627-847X)
- Alba Nicolau (ORCID: https://orcid.org/0000-0002-0836-2802)
- Ariadna Laguna (ORCID: https://orcid.org/0000-0002-9732-6677)
- Lluís Miquel-Rio (ORCID: https://orcid.org/0000-0002-3547-6004)
- Sébastien Arthaud (ORCID: https://orcid.org/0000-0001-7271-5468)
- Patrice Fort (ORCID: https://orcid.org/0000-0003-1211-8631)
- Annabelle Parent (ORCID: https://orcid.org/0000-0002-6195-812X)
- Miquel Vila (ORCID: https://orcid.org/0000-0002-1352-989X)
- Joan Compte (ORCID: https://orcid.org/0000-0001-5447-5122)
- Helena Xicoy (ORCID: https://orcid.org/0000-0001-6641-1222)
- Analı́a Bortolozzi (ORCID: https://orcid.org/0000-0002-2069-9192)
- Iria Carballo‐Carbajal (ORCID: https://orcid.org/0000-0002-4403-8006)
- Lydia Giménez‐Llort (ORCID: https://orcid.org/0000-0002-4091-489X)
- Jordi Romero‐Giménez (ORCID: https://orcid.org/0000-0002-8459-9895)
- Núria Peñuelas (ORCID: https://orcid.org/0000-0001-6443-9790)
- Marina Lorente Picón (ORCID: https://orcid.org/0000-0002-3629-9804)
- Thais Cuadros (ORCID: https://orcid.org/0000-0001-7376-7470)
- Jiong Liu (ORCID: https://orcid.org/0009-0001-2208-2882)
- Gemma Pujol
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Autònoma de Barcelona (ES)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Instituto de Salud Carlos III (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- Centre de Recherche en Neurosciences de Lyon (FR)
- Vall d'Hebron Institut de Recerca (ES)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Centre Hospitalier Le Vinatier (FR)
- Institut Català de Paleontologia Miquel Crusafont (ES)
- Réseau d'Allergo-Vigilance (FR)
- Research Network (United States) (US)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Medical Research Network (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1038/s41467-024-53168-7
- Citations
- 24
- Primary Topic
- melanin and skin pigmentation
- Type
- article
- Field-Weighted Citation Impact
- 7.50
Funders
- Michael J. Fox Foundation for Parkinson's Research
- European Molecular Biology Laboratory
- EU Joint Programme – Neurodegenerative Disease Research
- Fondation Neurodis
- Ministerio de Economía y Competitividad
- China Scholarship Council
- Ministerio de Ciencia e Innovación
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina
- Association France Parkinson
- Fundació Institut de Recerca Hospital Universitari Vall d’Hebron
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación