Objective: We aim to characterize the consequences of age-dependent intracellular neuromelanin accumulation in catecholaminergic neuronal populations to understand the relationship between this process and the vulnerability of these cells in Parkinson’s disease (PD), as well as its impact on healthy brain aging.
Background: PD is characterized by a preferential degeneration of neurons that accumulate with age the pigment neuromelanin, especially neurons from substantia nigra (SN) and locus coeruleus (LC). We previously generated a rat model exhibiting progressive unilateral SN production of neuromelanin that showed parkinsonian-like neuropathology and motor deficits1.
Method: We generated a new neuromelanin-producing rodent model, based on the tissue-specific constitutive expression of human tyrosinase (hTyr) under the tyrosine hydroxylase (TH) promoter (Tg-TH-hTyr), that mimics the bilateral distribution of pigmentation within the aging human brain (i.e. catecholaminergic groups A1-A142). We characterized the pathological and behavioral consequences of intracellular neuromelanin accumulation.
Results: In parallel to neuromelanin intracellular buildup, Tg-TH-hTyr mice exhibited major PD features, including motor and non-motor behavioral alterations, inclusion body formation and degeneration of specific catecholaminergic neuronal groups. Transcriptomic analysis of neuromelanin-laden neurons revealed alterations in PD-related biological pathways.
Conclusion: Modelling human neuromelanin accumulation in rodents leads to age-dependent catecholaminergic dysfunction and molecular alterations that correlate with motor and non-motor deficits, which is relevant to PD pathology and brain aging.
Part of this abstract has been presented in Brain Conference 2021 (4-5 March) and AD/PD 2021 (9-14 March).
References: 1Carballo-Carbajal I, Laguna A, Romero-Giménez J, Cuadros T, et al. (2019). Brain Tyrosinase Overexpression Implicates Age-Dependent Neuromelanin Production in Parkinson’s Disease Pathogenesis. Nat Commun 10(1):973. 2Bogerts B. 1981. A Brainstem Atlas of Catecholaminergic Neurons in Man, Using Melanin as a Natural Marker. J Comp Neurol 197(1):63–80.
To cite this abstract in AMA style:
N. Peñuelas, A. Laguna, M. Gonzalez-Sepulveda, LL. Miquel-Rio, N. Benseny-Cases, H. Xicoy, J. Compte, A. Nicolau, M. Lorente-Picón, E. álvarez-Marimon, J. Romero-Giménez, A. Parent, T. Cuadros, F. Cacho-Nerin, J. Cladera, A. Bortolozzi, I. Carballo-Carbajal, M. Vila. Age-dependent multisystem parkinsonian features in a novel neuromelanin-producing transgenic mouse model [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/age-dependent-multisystem-parkinsonian-features-in-a-novel-neuromelanin-producing-transgenic-mouse-model/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/age-dependent-multisystem-parkinsonian-features-in-a-novel-neuromelanin-producing-transgenic-mouse-model/