Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related neurodegenerative deficits
Laguna, Ariadna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Peñuelas, Núria (Vall d'Hebron Institut de Recerca (VHIR))
González Sepúlveda, Marta (Vall d'Hebron Institut de Recerca (VHIR))
Nicolau Vera, Alba (Vall d'Hebron Institut de Recerca (VHIR))
Arthaud, Sébastien (University Claude Bernard)
Guillard-Sirieix, Camille (Vall d'Hebron Institut de Recerca (VHIR))
Lorente-Picón, Marina (Vall d'Hebron Institut de Recerca (VHIR))
Compte, Joan (Vall d'Hebron Institut de Recerca (VHIR))
Miquel-Rio, Lluís (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Xicoy, Helena (Vall d'Hebron Institut de Recerca (VHIR))
Liu, Jiong (University Claude Bernard)
Parent, Annabelle (Vall d'Hebron Institut de Recerca (VHIR))
Cuadros, Thais (Vall d'Hebron Institut de Recerca (VHIR))
Romero-Giménez, Jordi (Vall d'Hebron Institut de Recerca (VHIR))
Pujol, Gemma (Vall d'Hebron Institut de Recerca (VHIR))
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Fort, Patrice (University Claude Bernard)
Bortolozzi, Analía (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Carballo-Carbajal, Iria (Vall d'Hebron Institut de Recerca (VHIR))
Vila Bover, Miquel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2024
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. Unlike humans, rodents do not accumulate the brain pigment neuromelanin in catecholamine neurons with age. The transgenic mouse model here presented accumulates neuromelanin and mimics the early physiopathology of Parkinson's disease.
Grants:	Agencia Estatal de Investigación PID2022-141700OB-I00 "la Caixa" Foundation LCF/BQ/DI18/1166063 "la Caixa" Foundation LCF/PR/HR17/52150003 Instituto de Salud Carlos III AC20/00121 Agencia Estatal de Investigación BES-2017-080191
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Neural ageing ; Parkinson's disease
Published in:	Nature communications, Vol. 15 (october 2024) , ISSN 2041-1723

DOI: 10.1038/s41467-024-53168-7
PMID: 39394193

18 p, 5.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles